Novel pharmaceutical composition for treating dry eye

Abstract

The present invention provides a novel pharmaceutical composition for treating dry eye, which can repair damaged cornea and increase tear secretion by significantly improving corneal damage and corneal opacity without side effects, thereby effectively treating ophthalmic diseases related to dry eye.

Description

Technical Field

[0001] The present invention relates to a novel pharmaceutical composition for treating dry eye, and more particularly to a novel pharmaceutical composition for treating dry eye that can treat ophthalmic diseases associated with dry eye without side effects. Background Art

[0002] Dry eye syndrome is a syndrome characterized by symptoms such as foreign body sensation, burning sensation, or eye irritation, which usually occur due to decreased tear production or increased tear film loss caused by tear evaporation. Existing treatments for dry eye syndrome focus on maintaining a certain amount of tears by dripping artificial tears as artificial tears or temporarily or permanently blocking the tear ducts to compensate for insufficient tears according to symptoms. However, such symptomatic treatments are not effective enough and cannot directly eliminate the cause of the disease. Therefore, the recent trend in the treatment of dry eye syndrome tends to be a direct and ultimate treatment method that improves dry eyes by reducing inflammation of the tear glands and the surface of the eyeball, rather than passive treatment aimed at relieving symptoms. In addition, for moderate to severe dry eye syndrome that is difficult to regulate with artificial tears, anti-inflammatory drugs such as cyclosporine, steroids, and autologous serum eye drops are being used in combination as drugs for controlling inflammation rather than simply prescribing artificial tears. However, artificial tears have the disadvantages of being used several times a day because the effect is temporary and having no protective effect on corneal damage. When steroid preparations are used for a long time, they may induce fatal side effects such as glaucoma. Cyclosporine, a broad-spectrum immunosuppressant, also has limitations such as eye pain, burning sensation, foreign body sensation, congestion, and some systemic side effects. In addition, therapeutic contact lenses are inconvenient to use and may become a cause of infection. The closed lacrimal point surgery has the disadvantages of rejection of surgery and difficulty in restoring the original state when side effects occur. Therefore, there is an urgent need to develop a preparation that can effectively prevent or treat dry eye without side effects. In this regard, Korean Patent Publication No. 2014-0099526 discloses the use of a cell-permeable peptide inhibitor of the JNK signal transduction pathway for the treatment of dry eye. Summary of the invention

[0003] (Technical issues to be resolved)

[0004] However, in the case of the above-mentioned prior art, there is a high possibility of inducing local irritation to the ocular mucosa, and it is difficult to quantitatively administer the drug, which may significantly reduce the treatment efficiency.

[0005] The present invention is proposed to solve various problems including the above-mentioned problems, and its purpose is to provide a novel pharmaceutical composition for treating dry eye, which effectively treats dry eye by significantly inhibiting the reduction of tear secretion and changes in corneal morphology caused by dry eye without side effects. However, these problems are only exemplary, and the scope of the present disclosure is not limited thereto.

[0006] (Solution to the problem)

[0007] According to one aspect of the present invention, there is provided a pharmaceutical composition for treating and preventing dry eye, the composition comprising a peptide having antibacterial activity as an active ingredient, the peptide consisting of seven amino acids, the peptide comprising an amino acid sequence selected from the group consisting of:

[0008] BOBW

[0009] (wherein B is a basic amino acid each optionally selected from the group consisting of lysine (K) or arginine (R), and O is an aromatic amino acid each optionally selected from the group consisting of phenylalanine (F) or tryptophan (W)).

[0010] According to another aspect of the present invention, there is provided a pharmaceutical composition for treating keratoconjunctivitis, the composition comprising a peptide having antibacterial activity as an active ingredient, the peptide consisting of seven amino acids, the peptide comprising an amino acid sequence selected from the group consisting of:

[0011] BOBW

[0012] (wherein B is a basic amino acid each optionally selected from the group consisting of lysine (K) or arginine (R), and O is an aromatic amino acid each optionally selected from the group consisting of phenylalanine (F) or tryptophan (W)).

[0013] According to another aspect of the present invention, there is provided a pharmaceutical composition for improving corneal damage and corneal opacity, the composition comprising a peptide having antibacterial activity as an active ingredient, the peptide consisting of seven amino acids, the peptide comprising an amino acid sequence selected from the group consisting of:

[0014] BOBW

[0015] (wherein B is a basic amino acid each optionally selected from the group consisting of lysine (K) or arginine (R), and O is an aromatic amino acid each optionally selected from the group consisting of phenylalanine (F) or tryptophan (W)).

[0016] According to another aspect of the present invention, a method for treating dry eye in a subject is provided, the method comprising the step of administering the composition to the subject suffering from dry eye.

[0017] According to another aspect of the present invention, there is provided a use of a peptide in the preparation of a therapeutic agent for dry eye, wherein the peptide has antibacterial activity and is composed of seven amino acids, and the peptide includes an amino acid sequence selected from the group consisting of:

[0018] BOBW

[0019] (wherein B is a basic amino acid each optionally selected from the group consisting of lysine (K) or arginine (R), and O is an aromatic amino acid each optionally selected from the group consisting of phenylalanine (F) or tryptophan (W)).

[0020] (Effects of the Invention)

[0021] As described above, the novel dry eye treatment pharmaceutical composition of the present invention significantly inhibits the reduction of tear secretion, keratoconjunctivitis and changes in corneal morphology caused by dry eye, thereby having excellent effects of repairing damaged cornea and increasing tear secretion, and can therefore be used to develop a safe and effective dry eye treatment agent. Of course, the scope of the present invention is not limited by such effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 These are images of the extent of corneal damage obtained by fluorescent staining and microscopy after the peptide of the present invention was treated in a mouse model.

[0023] Figure 2 is a graph quantifying and analyzing the extent of corneal damage treated with the peptides according to the present invention.

[0024] Figure 3 This is an image of the turbidity of the eyeball taken under a microscope after the peptide of the present invention was treated in a mouse model.

[0025] Figure 4 is a graph quantifying and analyzing the opacity of the eye treated with the peptide according to the present invention. DETAILED DESCRIPTION

[0026] The term "antimicrobial peptide" used in this article generally refers to a cationic peptide compound composed of a relatively simple structure, which has a broad antibacterial spectrum against gram-positive bacteria, gram-negative bacteria, fungi, viruses, etc. Although its mechanism of action has not been fully revealed, it is well known that the compound exhibits antibacterial activity by destroying the cell membrane of microorganisms.

[0027] The term "dry eye syndrome" as used in this article refers to an eye disease caused by insufficient tears, excessive evaporation of tears, or an imbalance in the composition of tears, which leads to damage to the surface of the eye, eye soreness, and irritation symptoms such as irritation, foreign body sensation, dryness, etc., and inflammation of the tears and the surface of the eye (cornea and conjunctiva), rather than simply insufficient tears, which leads to eye discomfort, decreased vision, instability of the tear layer, and damage to the surface of the eye, increasing the risk of pain attacks, irregular corneal surface, blurred and fluctuating vision, and corneal ulcers.

[0028] The term "corneal opacity" used herein refers to a state in which an opaque portion is formed on the cornea, which is a normally transparent tissue, or a state in which the entire cornea becomes opaque due to surface dryness, damage, inflammation, or the like.

[0029] (Detailed description of the present invention)

[0030] According to one aspect of the present invention, there is provided a pharmaceutical composition for treating and preventing dry eye, the composition comprising a peptide having antibacterial activity as an active ingredient, the peptide consisting of seven amino acids, the peptide comprising an amino acid sequence selected from the group consisting of:

[0031] BOBW

[0032] (wherein B is a basic amino acid each optionally selected from the group consisting of lysine (K) or arginine (R), and O is an aromatic amino acid each optionally selected from the group consisting of phenylalanine (F) or tryptophan (W)).

[0033] In the pharmaceutical composition, the dry eye may be aqueous tear deficiency dry eye or evaporative dry eye. In this case, the aqueous tear deficiency dry eye refers to the dry eye caused by insufficient tear secretion by the lacrimal gland, and the evaporative dry eye refers to the dry eye caused by excessive water loss from the exposed ocular surface when the lacrimal gland secretion function is normal. In addition, an octanoyl group may be added to the N-terminus of the peptide or an amine group may be added to the C-terminus.

[0034] According to another aspect of the present invention, there is provided a pharmaceutical composition for treating keratoconjunctivitis, the composition comprising a peptide having antibacterial activity as an active ingredient, the peptide consisting of seven amino acids, the peptide comprising an amino acid sequence selected from the group consisting of:

[0035] BOBW

[0036] (wherein B is a basic amino acid each optionally selected from the group consisting of lysine (K) or arginine (R), and O is an aromatic amino acid each optionally selected from the group consisting of phenylalanine (F) or tryptophan (W)).

[0037] According to another aspect of the present invention, there is provided a pharmaceutical composition for improving corneal damage and corneal opacity, the composition comprising a peptide having antibacterial activity as an active ingredient, the peptide consisting of seven amino acids, the peptide comprising an amino acid sequence selected from the group consisting of:

[0038] BOBW

[0039] (wherein B is a basic amino acid each optionally selected from the group consisting of lysine (K) or arginine (R), and O is an aromatic amino acid each optionally selected from the group consisting of phenylalanine (F) or tryptophan (W)).

[0040] In the pharmaceutical composition, the corneal damage and corneal opacity may be caused by dry eye or keratoconjunctivitis, and the pharmaceutical composition may have a preparation selected from the group consisting of ointments, external skin preparations, aerosols, sprays, eye drops, oral preparations, and injections.

[0041] According to another aspect of the present invention, a method for treating dry eye in a subject is provided, the method comprising the step of administering the composition to the subject suffering from dry eye.

[0042] According to another aspect of the present invention, there is provided a use of a peptide in the preparation of a therapeutic agent for dry eye, wherein the peptide has antibacterial activity and is composed of seven amino acids, and the peptide includes an amino acid sequence selected from the group consisting of:

[0043] BOBW

[0044] (wherein B is a basic amino acid each optionally selected from the group consisting of lysine (K) or arginine (R), and O is an aromatic amino acid each optionally selected from the group consisting of phenylalanine (F) or tryptophan (W)).

[0045] The pharmaceutical composition according to the present invention may also include a pharmaceutically acceptable carrier or additive. The term "pharmaceutically acceptable" as used herein refers to a physiologically acceptable and generally does not cause allergic reactions such as gastrointestinal disorders, dizziness, or similar reactions when applied to humans. As examples of the additives, excipients, disintegrants, binders, lubricants, wetting agents, dispersants, stabilizers, etc. may be included. As examples of the excipients, lactose, mannitol, isomalt, microcrystalline cellulose, silicified microcrystalline cellulose, powdered cellulose, etc. may be included. As examples of disintegrants, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, sodium starch glycolate, cross-linked sodium carboxymethyl cellulose, starch, etc. may be included. As examples of binders, hydroxypropyl cellulose, hypromellose, polyvinylpyrrolidone, copolyvinylpyrrolidone, pregelatinized starch, etc. may be included. As examples of lubricants, stearic acid, magnesium stearate, sodium stearyl fumarate, etc. may be included. As examples of wetting agents, polyoxyethylene sorbitan fatty acid ester derivatives, poloxamer, polyoxyethylene castor oil derivatives may be included. Examples of dispersants include hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, sodium carboxymethyl cellulose, methyl cellulose, etc. Examples of stabilizers include citric acid, fumaric acid, succinic acid, etc. In addition, the pharmaceutical composition of the present invention may further include anticoagulants, flavoring agents, emulsifiers, preservatives, etc.

[0046] In addition, the pharmaceutical composition of the present invention can be formulated using methods known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The pharmaceutical preparation can be a powder, granules, tablet, suspension, emulsion, syrup, aerosol or soft or hard gelatin capsule.

[0047] The term "treatment" as used herein refers to all actions that alleviate or beneficially change the symptoms of dry eye by administering the composition of the present invention.

[0048] The administration routes of the pharmaceutical composition include oral, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal, for example, the pharmaceutical composition can be applied by topical application. The parenteral administration includes subcutaneous, intradermal, intravenous, intramuscular, intralesional injection or infusion techniques.

[0049] Pharmaceutical composition of the present invention can be administered with pharmaceutically effective amount.Term used in this article " pharmaceutically effective amount " refers to the sufficient amount of treating disease with the reasonable benefit / risk ratio applicable to any medical treatment, and the effective dose level can be determined according to factors including individual type and severity, age, individual sex, disease type, drug activity, sensitivity to drug, administration time, administration route and excretion rate, treatment time, the drug used in combination with pharmaceutical composition and other factors well-known in the medical field.Composition of the present invention can be used as subject therapeutic agent or administered in combination with other therapeutic agents, and can be administered sequentially or simultaneously with existing therapeutic agents.In addition, single dose or multiple dose administration is possible.Considering all the above factors, it is important to use the amount that can obtain the maximum effect in the minimum amount without side effects, and can be easily determined by those skilled in the art.

[0050] The dosage of the pharmaceutical composition can be varied in various ways according to various factors including the age, weight, general health, sex, administration time, administration route, excretion rate, drug combination and severity of a particular disease of the subject. In addition, the pharmaceutical composition of the present invention can be used alone or in combination with surgery, radiotherapy, hormone therapy, chemotherapy and methods using biological response modifiers. In addition, the pharmaceutical composition can be administered in a dosage range of 0.001 to 200 mg / kg based on an adult, and when the pharmaceutical composition is an external preparation, based on an adult, preferably in an amount of 1.0 to 3.0 mL, once to five times a day, for at least one month, but the dosage is not intended to limit the scope of the present invention.

[0051] Based on the peptides found through the existing basic screening, the present inventors synthesized modified peptides in which various lipid components such as palmitoyl and octanoyl were linked to the N-terminus of the peptides to further increase the antibacterial activity and permeability to show high antibacterial action and immunomodulatory activity, thereby developing a novel antibacterial and immunomodulatory peptide (hereinafter referred to as "Peptide I") that is effective in treating immune diseases such as atopic dermatitis and diseases caused by pathogenic bacteria infection (Korean Patent No. 1855170). However, as a result of applying the peptide to an animal model induced by dry eye, the present inventors confirmed a significant effect of improving corneal damage and corneal opacity compared with the control group, thereby completing the present invention.

[0052] Hereinafter, the present invention will be described in more detail by way of examples. However, the present invention is not limited to the following disclosed examples, but can be implemented in various forms, and these examples are provided to make the disclosure of the present invention complete and to fully inform those skilled in the art of the scope of the present invention.

[0053] Example 1: Preparation of immunomodulatory and antimicrobial peptides

[0054] The present inventors developed a peptide (KFKWRYm) having immunomodulatory function and antibacterial activity through conventional basic screening and retrieval, and obtained a patent for this (Korean Patent No. 10-1855170). Then, in order to develop an improved peptide having better immunomodulatory and antibacterial ability than the above-mentioned peptide, various variants were designed in the amino acid sequence of the above-mentioned patented peptide, and these peptides were synthesized using the usual amino acid synthesis method (Umbarger, HE, Ann. Rev. Biochem., 47: 533-606, 1978), and used as immunomodulatory and antibacterial candidate peptides. In addition, as described above, the present inventors added an octanoyl group or an acetyl group to the N-terminus of the above-mentioned synthesized peptide and / or modified the amino group instead of the C-terminal carboxyl group to be substituted.

[0055] Example 2: FPR2 activation and antibacterial activity experiments of novel peptides

[0056] In order to confirm whether the immunomodulatory and antimicrobial peptide candidates of the present invention have the function of activating the immunomodulatory function of the organism, the present inventors observed the changes in calcium ion permeability. Specifically, in order to confirm whether the peptide activates FPR2, the intracellular calcium ion concentration was measured. To this end, the present inventors used RBL cells that do not express FPR2 and RBL cells that overexpress FPR1 (FPR1-RBL) and RBL cells that overexpress FPR2 (FPR2-RBL) in a method capable of sensitively measuring intracellular free calcium ions and used a dye Fura-2 / AM that has a strong binding force to calcium. That is, cells were cultured in RPMI medium containing 10% fetal bovine serum, and in the mid-log phase (mid-log phase, 1-3×10 7 The cells were then washed several times with RPMI medium without fetal bovine serum and resuspended in RPMI medium until the concentration was 1×10 7 cells / mL. Then, add Fura-2 / AM at a final concentration of 3 μM and incubate in a 37°C, 5% CO2 incubator for 45 minutes while stirring continuously. After an appropriate period of time, harvest the cells, wash them several times with RPMI medium again, and then suspend them in an appropriate amount of RPMI medium supplemented with 250 μM sulfinpyrazone to prevent Fura-2 that has entered the cells from escaping to the outside of the cells. Take about 2×10 6The cells were harvested by rapid centrifugation and resuspended in 1 mL of Locke's solution to which EGTA but no calcium ions were added, and the absorbance ratio at two wavelengths, 340 nm and 380 nm, was monitored on a spectrophotometer. After treatment with different concentrations (1 μM, 0.1 μM and 0.01 μM) of the peptide according to the present invention at intervals of approximately 1 minute, the absorbance difference at the two wavelengths was examined and then converted into the concentration of calcium ions free into the cells according to the method of Grynkiewicz.

[0057] In addition, in order to determine the antibacterial activity of the peptide, Staphylococcus aureus ( Staphylococcus aureus ) and Pseudomonas aeruginosa ( Pseudomonas aeruginosa ), spread it on the agar plate medium 4 times and culture it in a 36°C incubator overnight. The next day, the strain colonies produced on the agar plate medium were inoculated into 3 mL of nutrient broth and cultured in a shaking incubator at 36°C and 220 rpm overnight. The next day, the above bacteria were diluted, the absorbance was measured at 600nm and the absorbance was adjusted to 0.5, and the bacteria were diluted in the nutrient broth at a ratio of 1:100. Then, the peptide prepared in the above example was diluted in the nutrient medium to concentrations of 0, 1.25, 2.5, 5, 10, 20 and 40 μM, respectively, and 1 mL was prepared, and then 1 mL of the diluted above bacteria was inoculated. Next, it was stirred and cultured at 36°C and 220 rpm for 18 hours, and then the absorbance was measured at 600nm.

[0058] As a result, most peptides showed FPR2 activation effects and were effective against Pseudomonas aeruginosa ( P.aeruginosa ) and Staphylococcus aureus ( S. aureus ) showed high antibacterial activity (Table 1). The FPR2 activation and antibacterial activity results of the above peptides are summarized in Table 1 below.

[0059] [Table 1]

[0060] FPR2 activation and antimicrobial activity of antimicrobial peptides

[0061]

[0062] Example 3: Animal model construction

[0063] In order to confirm the dry eye and inflammation improving effect of the peptide peptide I (SEQ ID NOs. 1 to 6) of the present invention, the present inventors constructed a mouse animal model. Specifically, 12-week-old male mice of the C57BL / 6 family were used as experimental animals, and 0.2% benzalkonium chloride was dripped into the eyes of the mice twice a day during the 15-day experimental period to induce dry eyes and keratoconjunctivitis, except for the control group (control) in which dry eyes were not induced. Thereafter, the degree of corneal damage of the mice was evaluated by corneal staining on the third day, and after selecting mice with sufficient corneal damage, the experimental groups were classified by randomized block design. Next, starting from the fourth day, 1 hour after the administration of 0.2% benzalkonium chloride, the peptide I of the present invention (0.005% and 0.01%) was dripped into the eyes at an interval of twice a day. The peptide I was dissolved in physiological saline according to the concentration of the administration solution, and Restasis (0.05% cyclosporin) commercially available from Allergan was administered as a positive control group, and physiological saline was administered as a negative control group.

[0064] Example 4: Effect of improving corneal damage

[0065] The present inventors investigated the therapeutic effect of administration of peptide I according to the present invention on dry eye and keratoconjunctivitis. Specifically, mice were anesthetized by inhalation with isoflurane on days 3, 7, 11 and 15 of dry eye induction (days 0, 4, 8 and 12 of administration), and then fluorescein as a fluorescence dye was instilled into the eyes of the mice for corneal staining. Then, the residual fluorescein was washed with saline, and then the eyeball was photographed with a fluorescence microscope to obtain an image, and the fluorescent staining area was calculated and quantified using an image analysis program (Image J) to evaluate the degree of corneal damage caused by dry eye and keratitis.

[0066] As a result, it was found that administration of the peptide I of the present invention significantly improved corneal damage at a lower concentration compared with the control group ( Figure 1 and 2 ).

[0067] Example 5: Effect of alleviating corneal opacity

[0068] The present inventors investigated the effect of administration of the peptide I according to the present invention on reducing opacity caused by corneal damage. Specifically, mice were anesthetized by inhalation of isoflurane on days 3, 7, 11, and 15 of dry eye induction (days 0, 4, 8, and 12 of administration), and then images of the eyeballs were obtained by photographing them with a microscope. The degree of corneal opacity was quantified and evaluated by assigning points from 0 to 4 points, with 0 points if there was no opacity and the iris was clearly visible, 1 point if partial mild opacity was confirmed, 2 points if partial opacity or overall mild opacity was confirmed, 3 points if overall corneal opacity was confirmed, and 4 points if severe opacity and well-developed blood vessels were observed.

[0069] As a result, it was found that administration of the peptide I of the present invention significantly reduced corneal opacity at a lower concentration than that of the control group ( Figure 3 and 4 ).

[0070] In summary, the result of applying the novel pharmaceutical composition for treating dry eye of the present invention to a mouse animal model is that, compared with the control group, corneal damage and corneal opacity are significantly reduced without side effects. Therefore, the composition can be used as a material for effectively treating dry eye by repairing damaged cornea and increasing tear secretion.

[0071] Although the present invention has been described with reference to the above embodiments, this is merely exemplary. It will be understood by those skilled in the art that various modifications and other equivalent embodiments may be made. Therefore, the true technical protection scope of the present invention shall be based on the technical ideas of the attached claims. <110> Nova Cell Technologies <120> Novel pharmaceutical composition for treating dry eye <130> PO22-5260-CN <160> 6 <170> KoPatentIn 3.0 <210> 1 <211> 7 <212> PRT <213> Artificial sequence <220> <223> Antimicrobial peptides <220> <221> VARIANT <222> (1) <223> Xaa is Lys or Arg. <220> <221> VARIANT <222> (2) <223> Xaa is Phe or Trp. <220> <221> VARIANT <222> (3) <223> Xaa is Lys or Arg. <220> <221> VARIANT <222> (7) <223> D-amino acids <400> 1 Xaa Xaa Xaa Trp Arg Tyr Met 1 5 <210> 2 <211> 7 <212> PRT <213> Artificial sequence <220> <223> Antimicrobial peptides <220> <221> VARIANT <222> (1) <223> Octanoyl group is added to the N-terminus <220> <221> VARIANT <222> (7) <223> D-amino acids <220> <221> VARIANT <222> (7) <223> C Amidation <400> 2 Lys Phe Lys Trp Arg Tyr Met 1 5 <210> 3 <211> 7 <212> PRT <213> Artificial sequence <220> <223> Antimicrobial peptides <220> <221> VARIANT <222> (7) <223> D-amino acids <220> <221> VARIANT <222> (7) <223> C Amidation <400> 3 Lys Phe Lys Trp Arg Tyr Met 1 5 <210> 4 <211> 7 <212> PRT <213> Artificial sequence <220> <223> Antimicrobial peptides <220> <221> VARIANT <222> (1) <223> Octanoyl group is added to the N-terminus <220> <221> VARIANT <222> (7) <223> D-amino acids <220> <221> VARIANT <222> (7) <223> C Amidation <400> 4 Lys Trp Lys Trp Arg Tyr Met 1 5 <210> 5 <211> 7 <212> PRT <213> Artificial sequence <220> <223> Antimicrobial peptides <220> <221> VARIANT <222> (1) <223> Octanoyl group is added to the N-terminus <220> <221> VARIANT <222> (7) <223> D-amino acids <220> <221> VARIANT <222> (7) <223> C Amidation <400> 5 Arg Trp Arg Trp Arg Tyr Met 1 5 <210> 6 <211> 7 <212> PRT <213> Artificial sequence <220> <223> Antimicrobial peptides <220> <221> VARIANT <222> (7) <223> D-amino acids <220> <221> VARIANT <222> (7) <223> C Amidation <400> 6 Arg Trp Arg Trp Arg Tyr Met 1 5

Claims

1. Use of a peptide consisting of the amino acid sequence of SEQ ID NO: 2 in the preparation of a therapeutic agent for treating keratoconjunctivitis.

2. Use of a peptide consisting of the amino acid sequence of SEQ ID NO: 2 in the preparation of a therapeutic agent for dry eye disease.

3. Use of a peptide consisting of the amino acid sequence of SEQ ID NO: 2 in the preparation of a therapeutic agent for improving corneal damage and corneal opacity.

4. The use according to claim 2, characterized in that: The dry eye syndrome is aqueous tear deficiency dry eye syndrome or evaporative dry eye syndrome.

5. The use according to claim 3, characterized in that: The corneal damage and corneal opacity are caused by dry eye or keratoconjunctivitis.

6. The use according to any one of claims 1 to 5, characterized in that An octanoyl group is added to the N-terminus of the peptide or an amine group is added to the C-terminus thereof.

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