EP-4741413-A1 - PEPTIDE HAVING ACTIVITY OF ALLEVIATING DRY EYE DISEASE AND USES THEREOF

Abstract

The peptide of the present disclosure has a binding capacity to PAC1R, promotes activation of a PAC1R signaling pathway, and induces neuroblast differentiation, thereby having a tear secretion promoting activity. In addition, the peptide of the present disclosure promotes expression and secretion of mucin which is a tear component in conjunctival goblet cells, and has an activity of inhibiting inflammatory response and cell damage in human corneal epithelial cells. The peptide of the present disclosure may be used as an active material for treatment, prevention, and improvement of dry eye disease.

Inventors

• CHUNG, YONG JI
• KIM, EUN MI
• LEE, EUNG JI

Assignees

• Caregen Co., Ltd.

Dates

Publication Date

20260513

Application Date

20240807

Claims (7)

1. A peptide comprising an amino acid sequence of SEQ ID NO: 1.
2. A pharmaceutical composition for treating or preventing dry eye disease comprising the peptide of claim 1 as an effective component.
3. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition has an activity of promoting tear secretion by one or more activities of the following activities: (i) having a binding capacity to a pituitary adenylate cyclase 1 receptor (PAC1R) and promoting activation of PAC1R signaling pathway; (ii) an activity of promoting movement of Aquaporin 5 (AQP5) protein to a plasma membrane; and (iii) an activity of inducing neuroblast differentiation.
4. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition has an activity of promoting expression and secretion of mucin in conjunctival goblet cells.
5. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition has an activity of inhibiting inflammatory response and cell damage in human corneal epithelial cells.
6. The pharmaceutical composition of claim 2, wherein the dry eye disease includes one or more diseases, disorders, or symptoms selected from the group consisting of evaporative dry eye, water-deficient dry eye, dry keratitis, keratoconjunctivitis sicca, and dysfunctional tear syndrome.
7. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition includes a solution, a suspension, or a gel appropriate for topical administration to the eye.

Description

TECHNICAL FIELD [CROSS-REFERENCE TO RELATED APPLICATION] This application claims the benefit of priority to Korean Patent Application No. 10-2023-0104783, filed in the Korean Intellectual Property Office on August 10, 2023, the entire contents of which are incorporated herein by reference. [TECHNICAL FIELD] The present disclosure relates to a novel peptide having an activity of improving dry eye disease and a use thereof. BACKGROUND ART Dry eye disease (dry eye syndrome) refers to a condition or disease in which dry symptoms occur in the cornea or conjunctiva of the eye due to decreased tear secretion or changes in tear components even in the case of normal tear secretion. Causes of dry eye disease are very diverse, for example, a decreased tear secretion or changes in tear components due to aging, decreased tear production due to diseases such as rheumatoid arthritis, Sjogren syndrome, lupus, scleriasis, diabetes, and vitamin A-deficiency, reduced mucus secretion due to chronic conjunctivitis, excessive tear evaporation due to hyperthyroidism, decreased tear production due to decreased female hormones, evaporation of tears due to taking medicines such as antibiotics and antihistamines, eye irritation from dry environments, smoke, dust, sunlight, wind, and the like, a decreased number of eye blinks, and the like. The dry eye disease starts from desiccating stress on the cornea and conjunctiva of the eye, and the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 is increased due to the desiccating stress. Accordingly, antigen presenting cells (APCs) around the cornea and conjunctival tissue of the eye are activated and then move to lymph nodes and induce differentiation of Th1 and Th17 cells. The differentiated Th1 and Th7 cells move to a lesion area again and promote the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-17, and IFN-γ to further intensify inflammation, and damages such as matrix degradation is induced by matrix metalloproteinases (MMPs) increased by the stimulation (Mucosal Immunol. 2009 Jul; 2(4): 375-6. Role of Th17 cells in the immunopathogenesis of dry eye disease). Pituitary adenylate cyclase-activating polypeptide (PACAP) is a peptide hormone in the body and as its receptor, VPAC1, VPAC2, and PAC1 receptors are known, and recently, the results of confirming an effect of improving dry eye disease by promoting tear secretion in lacrimal gland by PACAP/PAC1R mechanism activation in the dry eye disease animal model have been reported (Int J Mol Sci. 2022 Jan 8; 23(2): 664., Potential Therapeutic Role of Pituitary Adenylate Cyclase-Activating Polypeptide for Dry Eye Disease). In addition, the results of confirming that synthetic peptide derived from PACAP having a PAC1R-specific agonist activity has an activity of healing corneal damage and increasing tear secretion from the lacrimal gland have been reported (Invest Ophthalmol Vis Sci. 2015 Jul; 56(8): 4336-49., A New Recombinant PACAP-Derived Peptide Efficiently Promotes Corneal Wound Repairing and Lacrimal Secretion). Until now, PACAP has been confirmed to involve in improving symptoms of dry eye disease through an anti-inflammatory activity, a corneal damage inhibition activity, and a tear secretion inducing activity. [Related Art Document] [Non-patent Document] Mucosal Immunol. 2009 Jul;2(4):375-6.Int J Mol Sci. 2022 Jan 8;23(2) :664.Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4336-49. DISCLOSURE OF THE INVENTION TECHNICAL PROBLEM The present inventors studied and made effort in order to develop a stable and effective active material having an activity of improving dry eye disease. As a result, it was experimentally confirmed that a novel peptide synthesized by the present inventors has an excellent activity of improving dry eye disease through an activity of promoting tear secretion, an activity of promoting secretion of mucin which is a tear film component, an activity of preventing damage to corneal epithelial cells, and the like, thereby completing the present disclosure. Therefore, an aspect of the present disclosure provides a novel peptide having an activity of improving dry eye disease. Another aspect of the present disclosure provides a pharmaceutical composition for treating or preventing dry eye disease including the peptide as an effective component. TECHNICAL SOLUTION In order to accomplish the object of the present invention, The present disclosure provides a peptide comprising an amino acid sequence disclosed in SEQ ID NO: 1. The present disclosure provides a pharmaceutical composition for treating or preventing dry eye disease comprising the peptide as an effective component. Hereinafter, the present disclosure will be described in detail. Peptide and its activity According to an aspect of the present disclosure, a peptide comprising an amino acid sequence disclosed in SEQ ID NO: 1 is provided. [Amino acid sequence of SEQ ID NO: 1] TLKKNKRFSK The term "peptide" in the present specificat