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KR-102961448-B1 - COMPOSITIONS AND METHODS OF USING NINTEDANIB FOR TREATING OCULAR DISEASES WITH ABNORMAL NEOVASCULARIZATION

KR102961448B1KR 102961448 B1KR102961448 B1KR 102961448B1KR-102961448-B1

Abstract

A composition and method using nintedanib to treat abnormal neovascularization symptoms in the anterior part of the eye are disclosed.

Inventors

  • 니 진송
  • 양 롱

Assignees

  • 에이디에스 테라퓨틱스 엘엘씨

Dates

Publication Date
20260507
Application Date
20170526
Priority Date
20160602

Claims (8)

  1. A composition comprising an effective amount of nintedanib or a pharmaceutically acceptable salt thereof for treating ophthalmic signs accompanied by abnormal neovascularization in the anterior part of the eye of an individual, At this time, ophthalmic signs are atopic conjunctivitis; ocular hyperemia; ocular pemphigus; or contact lens-induced neovascularization, and, The above composition is in the form of a topical ophthalmic formulation.
  2. delete
  3. delete
  4. delete
  5. A composition according to claim 1, wherein the topical ophthalmic formulation is a solution, suspension, cream, ointment, gel, gel-forming liquid, suspension containing liposomes or micelles, spray formulation, or emulsion.
  6. A composition according to claim 1, wherein the topical ophthalmic formulation is a topical eye drop.
  7. delete
  8. In paragraph 6, the composition is a composition administered topically to the eyes of an individual.

Description

Compositions and methods of using nintedanib for treating ocular diseases with abnormal neovascularization Claim of priority This application claims the rights of U.S. provisional application serial number 62/344,878 filed June 2, 2016 and U.S. provisional application serial number 62/344,870 filed June 2, 2016, the full contents of each of which are incorporated herein by reference. Technology field The present disclosure relates to an ophthalmic composition and method using nintedanib to treat and prevent transplant rejection in high-risk corneal transplant patients and to treat ophthalmic diseases accompanied by abnormal neovascularization in the anterior part of the eye. Abnormal neovascularization accompanies many diseases of the anterior part of the eye. Abnormal neovascularization accompanies transplant rejection in high-risk corneal transplant patients. Current treatments for many of these indications require improvement. The method disclosed herein addresses the problems of current treatments and provides improved treatment for these diseases. summation In a specific embodiment, the present disclosure provides a method for treating an ophthalmic disease involving abnormal neovascularization of the anterior portion of the eye, the method comprising administering an effective amount of nintedanib or a pharmaceutically acceptable salt thereof to the eye of an individual requiring such treatment. In a specific embodiment, the disclosed method treats, prevents, or delays the onset of transplant rejection in a corneal transplant patient. For example, the disclosed method treats, prevents, or delays the onset of transplant rejection in a corneal transplant patient with a high risk of transplant rejection. In a specific embodiment, the disclosed method is performed before, simultaneously with, or after surgery to prevent transplant rejection in high-risk corneal transplants. In certain embodiments, nintedanib is administered in the form of a topical ophthalmic formulation applied topically to the affected eye. In certain embodiments, the concentration of nintedanib in the formulation is 0.001% to 10% by weight or volume of the total composition. For example, an aqueous composition contains 0.001%, 0.01%, 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, 5.0%, or up to 10% nintedanib. In certain embodiments, the topical ophthalmic formulation is a solution, suspension, gel, or emulsion. In another embodiment, nintedanib is administered in the form of a graft or a semi-solid sustained-release formulation applied to the affected eye. In certain embodiments, the amount of nintedanib in the graft is 1 μg to 100 mg. The term "entity" refers to an animal or human, or one or more cells derived from an animal or human. Preferably, the entity is a human. The entity may also include non-human primates. A human entity may be known as a patient. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention pertains. Methods and materials described herein for use in the present invention; and other suitable methods and materials known in the art may also be used. These materials, methods, and examples are for illustrative purposes only and are not intended to be limiting. All publications, applications, patents, sequences, database entries, and other literature mentioned herein are incorporated by reference in their entirety. In the event of a conflict, this specification shall prevail, including definitions. Other features and advantages of the present invention will be apparent from the following detailed description, drawings, and claims. FIG. 1 is a schematic diagram illustrating an exemplary mechanism for preventing transplant rejection in high-risk corneal transplant patients according to the present disclosure. Figures 2A and 2B are graphs showing reduced corneal angiogenesis in the presence of nintedanib in a rabbit corneal suture model. Figure 2A provides the results for Day 12, and Figure 2B provides the results for Day 14. The corneal angiogenic area for each treatment group is shown (CBT-1 = Nintedanib ophthalmic formulations: 0.2% CBT-1 BID, 0.2% CBT-1 TID; 0.05% CBT-1 BID, 0.05% CBT-1 TID; vehicle control TID. The T-test significance level comparing each group vs. vehicle is indicated by an asterisk. Corneal transplantation is a common surgical procedure. Although the overall success rate of corneal transplantation is high, transplant failure remains a problem in some high-risk patients. These patients exhibit high levels of inflammation and angiogenesis within the host body, leading to increased immune responses and allograft rejection (Yu et al. World J Transplant. 2016;6(1):10-27). Oral immunosuppressive drugs are sometimes used to reduce the risk of transplant failure, but they cause systemic side effects. The disclosed method will inhibit vascular endothelial growth factor ("VEGF") and platelet-derived growt