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CN-121971475-A - Application of miR-125b-5p inhibitor or antagonist in treatment and/or prevention of myopia and preparation

CN121971475ACN 121971475 ACN121971475 ACN 121971475ACN-121971475-A

Abstract

The application discloses an application of miR-125b-5p inhibitor or antagonist in treating and/or preventing myopia and a preparation thereof. The miR-125b-5p inhibitor or antagonist is used, and particularly has the advantages of low administration frequency and high safety, and can inhibit miR-125b-5p expression in sclera, increase expression of target gene tp53, remarkably reduce scleral fibroblast transdifferentiation and scleral remodeling, slow down diopter reduction and eye axis extension of guinea pig-shaped deprivation myopia, further prevent myopia occurrence and control myopia progression, and provide safer, effective and convenient prevention and control means for myopic patients, especially teenagers.

Inventors

  • WEI RUIHUA
  • ZHAN HONG
  • ZHU YING
  • DU BEI
  • YANG CHAO
  • WANG HANRU

Assignees

  • 天津医科大学眼科医院

Dates

Publication Date
20260505
Application Date
20250928

Claims (10)

  1. Use of a miR-125b-5p inhibitor or antagonist or a pharmaceutical composition comprising a miR-125b-5p inhibitor or antagonist for the preparation of a medicament for the treatment and/or prevention of myopia.
  2. 2. The use of claim 1, wherein the miR-125b-5p inhibitor or antagonist is for inhibiting expression of miR-125b-5p in the sclera or antagonizing competitive binding of miR-125b-5p to an endogenous miRNA in the sclera, inhibiting miR-125b-5p function; The miR-125b-5p inhibitor or antagonist is selected from one or more of miRNA inhibitor and miRNA antagomir.
  3. 3. The use of claim 1, wherein the miR-125b-5p inhibitor or antagonist is miR-125b-5p antagomir having the nucleic acid sequence set forth in SEQ ID No. 8.
  4. 4. The use according to claim 1, wherein the pharmaceutical composition comprises an effective dose of miR-125b-5p antagomir having the nucleic acid sequence set forth in SEQ ID No. 8, and a pharmaceutically-acceptable carrier.
  5. 5. The use according to any one of claims 1 to 4, wherein the formulation of the medicament is a systemic formulation or a topical formulation, in particular an ophthalmic formulation, optionally the systemic formulation comprises one of an intravenous formulation, a subcutaneous formulation, an intramuscular formulation; optionally, the ophthalmic formulation comprises one of an eye drop, an ophthalmic gel, an ophthalmic ointment, an ophthalmic injection, a drug eluting contact lens; The ophthalmic preparation is a solution containing miR-125b-5p antagomir with a nucleic acid sequence shown in SEQ ID NO. 8, wherein the solvent of the solution is selected from pure water, phosphate buffer solution and physiological saline solution, the solvent of the solution is pure water, and the concentration of miR-125b-5p antagomir in the solution containing miR-125b-5p antagomir with the nucleic acid sequence shown in SEQ ID NO. 8 is in the range of 5 mu M to 40 mu M, and the concentration of miR-125b-5p antagomir in the solution is further selected from 5 mu M to 10 mu M.
  6. 6. The use according to claim 5, wherein the single administration of miR-125b-5p antagomir in the ophthalmic preparation is in the range of 50 pmol to 4000 pmol, optionally 50 pmol to 1000 pmol, 50 pmol to 800 pmol, 50 pmol to 600 pmol, 50 pmol to 100 pmol, 50 pmol, 100 pmol, 200 pmol, 400 pmol or 600 pmol, and/or The administration frequency is 1 to 7 times per week, alternatively 1 to 3 times per week.
  7. 7. The use according to any one of claims 1 to 4, wherein the treatment and/or prevention of myopia comprises at least one of (1) slowing down the reduction in diopter strength of the myopic eye, (2) slowing down the extension of the ocular axis, (3) reducing scleral fibroblast transdifferentiation and scleral remodeling, and/or The treatment and/or prevention of myopia comprises at least one of (1) preventing the occurrence of myopia, (2) controlling progression of myopia, in particular progression to high myopia, and (3) reducing the risk of developing high myopia complications.
  8. 8. A formulation comprising an effective amount of miR-125b-5p antagomir having a nucleic acid sequence set forth in SEQ ID No. 8, and a pharmaceutically-acceptable carrier; Optionally, the preparation is a systemic preparation or a local preparation, especially an ophthalmic preparation, and optionally, the systemic preparation comprises one of intravenous preparation, subcutaneous preparation and intramuscular preparation; optionally, the ophthalmic formulation comprises one of an eye drop, an ophthalmic gel, an ophthalmic ointment, an ophthalmic injection, a drug eluting contact lens.
  9. 9. The formulation of claim 8, wherein the ophthalmic formulation is a solution comprising miR-125b-5p antagomir having a nucleic acid sequence set forth in SEQ ID NO. 8, optionally wherein the solvent of the solution is selected from one of pure water, phosphate buffer, physiological saline solution, and further optionally wherein the solvent of the solution is pure water; alternatively, the concentration of miR-125b-5p antagomir in the solution containing miR-125b-5p antagomir having a nucleic acid sequence shown in SEQ ID NO. 8 is in the range of 5 μm to 40. Mu.M, further alternatively 5 μm to 10. Mu.M.
  10. 10. The formulation of claim 8 or 9, wherein the single dose of miR-125b-5p antagomir in the ophthalmic formulation is in the range of 50 pmol to 4000 pmol, optionally 50 pmol to 1000 pmol, 50 pmol to 800 pmol, 50 pmol to 600 pmol, 50 pmol to 100 pmol, 50 pmol, 100 pmol, 200 pmol, 400 pmol or 600 pmol, and/or The administration frequency is 1 to 7 times per week, alternatively 1 to 3 times per week.

Description

Application of miR-125b-5p inhibitor or antagonist in treatment and/or prevention of myopia and preparation Technical Field The present disclosure relates to pharmaceutical technology, and more particularly to the use of miR-125b-5p inhibitors or antagonists in the preparation of medicaments for treating and/or preventing myopia, and to formulations comprising miR-125b-5p inhibitors or antagonists. Background Myopia has become a global public health problem, and world health organization data show that the number of people with myopia in the world continuously rises, and the incidence rate of teenager myopia is particularly prominent. The existing myopia prevention and control means such as frame glasses and contact lenses can correct vision and control myopia progression, but have the problems of different control effects, higher price and the like, cornea shaping lenses can temporarily improve vision, but have the problems of infection risk and poor child compliance, and the laser surgery is not suitable for minors. In addition, the low-concentration atropine eye drops have a certain effect on myopia control, but have high use frequency, namely, 1-2 times per day, and have side effects of reduced regulating power, rebound and the like after long-term use. Therefore, the development of myopia control drugs which are safe, effective, have other action targets and are convenient to administer has important significance. Disclosure of Invention The inventor finds that miR-125b-5p expression is obviously increased in a sclera of a shape deprivation myopia guinea pig and a hypoxia cultured human sclera fibroblast myopia model, miR-125b-5p inhibitor or antagonist, especially miR-125b-5p antagomir with a nucleic acid sequence shown as SEQ ID NO:8, inhibits miR-125b-5p expression in the sclera, increases expression of a target gene tp53, can obviously reduce sclera fibroblast transdifferentiation and sclera remodeling, slows down diopter reduction and eye axis extension of the guinea pig shape deprivation myopia eye, further can prevent myopia occurrence, control myopia progression, and has the advantages of low administration frequency and high safety, thereby providing safer, effective and convenient prevention and control means for myopic patients, especially teenagers. Based on this, in a first aspect, embodiments of the application provide the use of a miR-125b-5p inhibitor or antagonist or a pharmaceutical composition comprising a miR-125b-5p inhibitor or antagonist in the preparation of a medicament for treating and/or preventing myopia. In some embodiments, the miR-125b-5p inhibitor or antagonist is used to inhibit expression of miR-125b-5p in the sclera or antagonizes miR-125b-5p from competitively binding to an endogenous miRNA in the sclera, inhibiting miR-125b-5p function. The miR-125b-5p inhibitor or antagonist can be selected from miRNA antagomir and miRNA inhibitor. In some embodiments, the miR-125b-5p inhibitor or antagonist is miR-125b-5p antagomir, which has a nucleic acid sequence shown in SEQ ID NO:8, i.e., the unmodified nucleic acid sequence is 5'-UCACAAGUUAGGGUCUCAGGGA-3', the modified nucleic acid sequence is subjected to cholesterol modification from the 5' end to the 3' end of the sequence, the two phosphodiester bonds at the 5' end are thio-modified to phosphorothioate diester bonds, the four phosphodiester bonds at the 3' end are thio-modified to phosphorothioate diester bonds, and the whole chain is subjected to 2' -methoxy modification. The miR-125b-5p antagomir can inhibit miR-125b-5p expression in sclera, increase expression of a target gene tp53, reduce scleral remodeling, and slow down diopter reduction and eye axis extension of guinea pig-shaped deprivation myopia. In some embodiments, the pharmaceutical composition comprises an effective dose of miR-125b-5p antagomir having a nucleic acid sequence set forth in SEQ ID NO. 8, and a pharmaceutically-acceptable carrier. In some embodiments, the formulation of the drug is a systemic formulation (e.g., intravenous, subcutaneous, intramuscular, etc.) or a topical formulation, particularly an ophthalmic formulation. In some embodiments, the ophthalmic formulation comprises an eye drop, an ophthalmic gel, an ophthalmic ointment, an ophthalmic injection, a drug eluting contact lens. In some embodiments, the ophthalmic formulation is a solution comprising miR-125b-5p antagomir having a nucleic acid sequence as set forth in SEQ ID NO. 8, optionally one of pure water, phosphate buffer, physiological saline solution or the like, and further optionally the solvent of the solution is pure water. In some embodiments, the concentration of miR-125b-5p antagomir in the solution containing miR-125b-5p antagomir having a nucleic acid sequence set forth in SEQ ID NO. 8 is in the range of 5. Mu.M to 40. Mu.M, further alternatively 5. Mu.M to 10. Mu.M. In some embodiments, the single dose of miR-125b-5p antagomir in the ophthalmic formulation ranges fro