WO2013100660A2 - Pharmaceutical composition for treatment of eye pain, containing pge2 synthesis inhibitor - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the treatment of eye pain, containing a PGE2 synthesis inhibitor. The use of the pharmaceutical composition for the prevention or treatment of eye pain according to the present invention, which contains the PGE2 synthesis inhibitor as an active ingredient, makes it possible to alleviate the symptoms of eye pain by selectively inhibiting the PGE2 expression level, and also has the advantages of treating and preventing xerophthalmia and of overcoming and preventing eye discomfort caused by various inflammation-inducing circumstances including following surgery. Also, by using a kit for detecting the amount of PGE2, PGD2 and COX2, the present invention makes it possible to easily diagnose eye-pain symptoms in clinical practice, and can be widely used in checking the state not only of patients having xerophthalmia but also patients following eye surgery.

Description

Pharmaceutical composition for treating eye pain comprising PPE2 synthesis inhibitor

The present invention relates to a pharmaceutical composition for treating ocular pain comprising a PGE2 synthesis inhibitor.

Dry eye syndrome is a very common disease with a prevalence of 5.5-15%, depending on the study population, age, and diagnostic criteria used in various epidemiologic studies worldwide. The disease is characterized by eye pain, irregular corneal surfaces, blurred and fluctuating vision, and increased risk of corneal ulcers. Altered corneal permeability in chronic dry eye and dry keratitis derived from an unstable tear film has been known to cause inflammation, which is due to an increase in inflammation-mediated chemokines and cytokines in the tear, immune activity by conjunctival epithelium and adhesion molecules ( Increased expression of HLA-DR and intercellular adhesion molecule [ICAM-1]), and increased T lymphocyte counts in the conjunctiva. Corneal ulcers resulting from keratoconjunctivitis sicca (KCS) can cause vision loss, vision loss and even eye loss. The concentration and activity of matrix metalloproteinase-9 (MMP-9) has been reported to increase significantly in the corneal epithelium and tear of experimental dry eye (EDE) mice as well as in tears of dry eye patients. Dry eye syndrome generally causes tears or fluctuations in the composition of the tear film, causing various uncomfortable symptoms. Recently, a new form of dry eye syndrome has been developed due to diseases caused by changes in tear film composition and neurogenic factors such as dry eye syndrome after LASIK (American Journal of Ophthalmology, 140 507, 2005).

Dry eye syndrome is found in more than 50% of all patients who visit ophthalmologists, and the elderly population, especially more than 70 to 80% of women who pass menopause, complain of eye discomfort due to dry eye syndrome. In the past, the cause of dry eye was thought to be due to the lack of aqueous layer due to decreased tear production in the tear glands, but recently, the inflammatory response or endogenous inflammatory response due to external stimulation has been found to be the primary cause. Chronic ocular surface damage caused by disorder of epithelial cells and degradation of the interaction between corneal epithelial cells and corneal parenchymal cells has been a problem. Dry eye may be caused by aging, hormonal changes, environmental factors (wind, heat, dust, tobacco smoke, hair dryers), reduction of eye blink frequency (VDT syndrome), contact lens wear, LASIK, cause of medication It can be caused by a variety of causes, including immune diseases (lupus, rheumatoid arthritis and Sjogren's syndrome) (American Journal of Ophthalmology, 137, 337-342, 2004).

On the other hand, NASAID, a non-specific COX enzyme inhibitor used to reduce inflammation, has an effect of non-specifically reducing prostaglandin levels. The drug is known to reduce inflammation and reduce pain, but it is also known to cause additional activation to produce leukotrienes, lipoxins and hydroperoxyeicosatetraenoic acids. In the ophthalmic area, non-specific COX enzyme inhibitors have been developed and used as eye drops, but serious side effects such as corneal perforation have been reported to the academic community by activation of the additional inflammatory products specified above.

Therefore, the present inventors have made intensive efforts to develop a pharmaceutical composition for treating or preventing ocular diseases causing eye pain, including dry eye syndrome, and thus, expression of PGE2 (prostaglandin E2) in the tears of patients with ocular pain symptoms compared to normal people. It was confirmed that the level is high, and when the PGE2 synthesis inhibitor was applied to an animal model, it was confirmed that the eye pain treatment effect was completed and the present invention was completed.

An object of the present invention to provide a pharmaceutical composition for preventing or treating ocular pain comprising PGE2 synthesis inhibitor as an active ingredient, and to provide a kit for diagnosing ocular pain, which can measure the level of PGE2.

According to the present invention, on the basis of a high level of PGE2 and a low level of PGD2 in tears of a patient with ocular pain symptoms, the present invention provides a pharmaceutical composition for preventing or treating ocular pain comprising PGE2 synthesis inhibitor as an active ingredient, A method of screening for reducing ocular pain relief agents is provided. Furthermore, PGE2, PGD2 and COX2 levels may be measured in the tears of patients to provide kits for diagnosing eye pain and information for diagnosing eye pain.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of eye pain comprising PGE2 synthesis inhibitor as an active ingredient.

The present invention provides a dietary supplement for preventing or improving ocular pain, comprising as an active ingredient a PGE2 synthesis inhibitor in another embodiment.

In the present invention, the PGE2 synthesis inhibitor is 5-Deoxy-A12, 14-PGJ2, Exisulind, NS-398, Leukotnene C4, mk-886, Analogues of MK-886, MF63, Thienopyrrole, Naphthalene disulphonamide, Resveratrol and γ- It may be characterized in that it is selected from the group consisting of hydroxybutenolide.

In the present invention, the pharmaceutical composition may be characterized by reducing the expression level of PGE2.

In addition, in the present invention, the eye pain may be characterized in that the eye pain due to dry eye, inflammatory eye disease or the use of contact lenses.

In the present invention, the pharmaceutical composition may be in the form of suspensions, powders, powders, granules, tablets, sustained release preparations, injections, ointments, eye drops, capsules, contact lens cleaners or contact lens lubricants, The composition may be characterized as targeting humans.

In the present invention, the health functional food may be characterized in that the capsule, tablets, granules, powder or beverage form.

In another embodiment, (a) contacting a sample to be analyzed with a cell comprising the PGE2 protein represented by SEQ ID NO: 1;

(b) measuring the amount or activity of the protein; And

(c) providing a method of screening an ocular pain relief agent comprising determining that the sample is a substance that alleviates ocular pain when the amount or activity of the protein is determined to be modulated.

In another embodiment, (a) contacting a sample to be analyzed with a cell comprising a gene encoding the PGE2 protein represented by SEQ ID NO: 1;

(b) measuring the expression level of the gene; And

(c) providing a method for screening an ocular pain relief agent, comprising determining that the sample is a substance that alleviates ocular pain when the expression level of the gene is measured to be controlled to be reduced, and the gene encoding the PGE2 protein is It may be characterized by represented by SEQ ID NO: 2.

In another embodiment, (a) contacting a sample to be analyzed with a cell comprising the COX2 protein represented by SEQ ID NO: 3;

(b) measuring the amount or activity of the protein; And

(c) providing a method of screening an ocular pain relief agent comprising determining that the sample is a substance that alleviates ocular pain when the amount or activity of the protein is determined to be modulated.

In another embodiment, (a) contacting a sample to be analyzed with a cell comprising a gene encoding the COX2 protein represented by SEQ ID NO: 3;

(b) measuring the expression level of the gene; And

(c) providing a method of screening an ocular pain relief agent, comprising determining that the sample is a substance that alleviates ocular pain when the expression level of the gene is measured to be controlled to be reduced, and the gene encoding the COX2 protein is It may be characterized by represented by SEQ ID NO: 4.

In yet another embodiment, the present invention provides a pharmaceutical composition for preventing or treating ocular pain, including the COX2 inhibitor as an active ingredient.

In yet another embodiment, the present invention provides a method of preparing a biologically-modified product, comprising: (a) measuring the level of PGE2 represented by SEQ ID NO: 1 from a biological sample isolated from a patient;

(b) providing an information providing method for diagnosing ocular pain, comprising comparing the level of PGE2 with that of a normal control sample.

In the present invention, the information providing method may further comprise the step of measuring the level of PGD2 or COX2 and comparing with the level of the normal control sample. At this time, when the PGE2 and COX2 levels are overexpressed than the normal control, and the PGD2 level is lower than the normal control, eye pain may be determined.

In still another embodiment, the present invention provides a kit for diagnosing or predicting eye pain, which includes an antibody that specifically binds to a protein attached to PGE2.

In the present invention, the kit for diagnosing or predicting eye pain may further include an antibody specifically binding to a protein attached to PGD2 or a protein attached to COX2.

The kit is characterized in that it comprises an antibody that attaches a protein for detection to PGE2, PGD2 and COX2 and specifically binds to the adhesion protein. The attached protein may be horseradish peroxidase, alkaline phosphatase or β-galactosidase.

In the present invention, the levels of PGE2, PGD2 and COX2 are enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry. It may be characterized by measuring by (LC-MS) or LC-MS / MS.

The composition of the present invention may be prepared as a pharmaceutical composition, a neutraceutical composition or a food composition.

When the composition of the present invention is made into a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical compositions of the present invention are those commonly used in the preparation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like It doesn't happen. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995). The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, mucosal administration, and eyedrop administration.

Suitable dosages of the pharmaceutical compositions of the present invention may vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to response of the patient. Can be. The dosage of the pharmaceutical composition of the present invention may be 0.001-100 mg / kg body weight, 0.01-80 mg / kg body weight, 0.1-60 mg / kg body weight per day on an adult basis. In addition, depending on the judgment of the doctor or pharmacist may be divided administration once a day to several times. In particular, in the case of eye drop administration, the formulation of 0.001 to 3% (w / v, below), preferably about 0.01 to 1%, is applied once to several times per day.

The pharmaceutical and health food composition of the present invention may be formulated by using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by those skilled in the art. It may be prepared in a dosage form or incorporated into a multi-dose container.

According to an embodiment of the present invention, the formulation of the composition of the present invention is a solution, suspension, syrup, emulsion, liposome, extract, powder, powder, granule, tablet, sustained release eye drop, capsule, contact It is a lens cleaner and a contact lens lubricant, and may further include a dispersant or stabilizer.

In the present invention, "diagnosis" refers to identifying the presence or characteristics of a pathological condition, determining the susceptibility of an object to a specific disease or condition, determining whether an object currently has a particular disease or condition. And determining the prognosis of one subject with a particular disease or condition.

As used to refer to the screening methods of the present invention, the term "sample" refers to an unknown candidate used in screening to test whether it affects the expression level of a gene or affects the amount or activity of a protein. . The sample includes, but is not limited to, chemicals, nucleotides, antisense-RNAs and natural extracts.

Measurement of the change in the expression level of the gene can be carried out through various methods known in the art. For example, RT-PCR (Sambrook et al., Molecular Cloning. A Laboratory Manual, 3rd ed. Cold Spring Harbor Press (2001)), Northern blotting (Peter B. Kaufma et al., Molecular and Cellular Methods in Biology and Medicine , 102-108, CRC press), hybridization reaction using cDNA microarray (Sambrook et al., Molecular Cloning.A Laboratory Manual, 3rd ed. Cold Spring Harbor Press (2001)) or in situ hybridization reaction (Sambrook et al. , Molecular Cloning.A Laboratory Manual, 3rd ed.Cold Spring Harbor Press (2001)).

When performed according to the RT-PCR protocol, first, total RNA is isolated from cells treated with a sample, and then single-stranded cDNA is prepared using oligo dT primers and reverse transcriptase. Then, single-stranded cDNA is used as a template, and PCR reaction is performed using a gene-specific primer set. Gene-specific primer sets are listed in Table 2 below. Then, the PCR amplification product is electrophoresed, and the formed band is analyzed to measure the change in the expression level of the gene.

Changes in the amount of protein can be carried out through various immunoassay methods known in the art. Examples include, but are not limited to, radioimmunoassay, radioimmunoprecipitation, immunoprecipitation, enzyme-linked immunosorbentassay (ELISA), capture-ELISA, inhibition or hardwood assays, and sandwich assays. The immunoassay or method of immunostaining is described in Enzyme Immunoassay, ET Maggio, ed., CRC Press, Boca Raton, Florida, 1980; Gaastra, W., Enzyme-linked immunosorbent assay (ELISA), in Methods in Molecular Biology, Vol. 1, Walker, JM ed., Humana Press, NJ, 1984; And Ed Harlow and David Lane, Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, 1999. For example, when the method of the present invention is carried out in accordance with radioimmunoassay methods, protein-specific antibodies labeled with radioisotopes (eg, C ¹⁴ , I ¹²⁵ , P ³² and S ³⁵ ) can be used. When the method of the present invention is carried out in an ELISA manner, certain embodiments of the present invention comprise the steps of: (a) coating an extract from the cells to which the sample has been treated on the surface of the solid substrate; (b) reacting the protein-specific antibody with the cell extract; (c) reacting the resultant of step (b) with a secondary antibody to which an enzyme is bound; And (d) measuring the activity of the enzyme. Suitable as the solid substrate are hydrocarbon polymers (eg polystyrene and polypropylene), glass, metals or gels, most preferably microtiter plates. Enzymes bound to the secondary antibody include, but are not limited to, enzymes that catalyze color reaction, fluorescence, luminescence or infrared reaction, for example, alkaline phosphatase, β-galactosidase, hose Radish peroxidase, luciferase and cytochrome P450. When alkaline phosphatase is used as the enzyme binding to the secondary antibody, bromochloroindolyl phosphate (BCIP), nitro blue tetrazolium (NBT), naphthol-ASB1-phosphate (naphthol-AS-B1) as a substrate chloronaphthol, aminoethylcarbazole, diaminobenzidine, D-luciferin, lucigenin (bis-N) when colorimetric substrates such as -phosphate) and enhanced chemifluorescence (ECF) are used, and horse radish peroxidase is used. -Methylacridinium nitrate), resorupin benzyl ether, luminol, amplex red reagent (10-acetyl-3,7-dihydroxyphenoxazine), TMB (3,3,5,5-tetramethylbenzidine), ABTS Substrates such as (2,2'-Azine-di [3-ethylbenzthiazoline sulfonate]) and o-phenylenediamine (OPD) can be used. Measurement of the final enzyme activity or signal in the ELISA method can be carried out according to various methods known in the art. If biotin is used as a label, the signal can be easily detected with streptavidin and luciferin if luciferase is used.

For use as a diagnostic kit, PGE2, PGD2 and COX2 are preferably detectably labeled. Various methods available for labeling biomolecules are well known to those skilled in the art and are contemplated within the scope of the present invention. Such methods include Tijssen, 'Practice and theory of enzyme immuno assays', Burden, RH and von Knippenburg (Eds), Volume 15 (1985), 'Basic methods in molecular biology'; Davis LG, Dibmer MD; Battey Elsevier (1990), Mayer et al., (Eds) 'Immunochemical methods in cell and molecular biology' Academic Press, London (1987), or in the series 'Methods in Enzymology', Academic Press, Inc.

There are many other markers and marking methods known to those skilled in the art. Examples of marker types that can be used in the present invention include enzymes, radioisotopes, colloidal metals, fluorescent compounds, chemiluminescent compounds and bioluminescent compounds.

Commonly used markers include phosphors (eg, fluresin, rhodamine, Texas red, etc.), enzymes (eg, horseradish peroxidase, β-galactosidase, alkaline phosphatase), radioisotopes (eg, 32 P or 125I), biotin, digoxigenin, colloidal metals, chemiluminescent or bioluminescent compounds (eg, dioxetane, luminol or acridinium). Labeling methods such as covalent binding of enzymes or biotinyl groups, iodide methods, phosphorylation methods, biotinylation methods and the like are well known in the art.

Detection methods include, but are not limited to, autoradiography, fluorescence microscopy, direct and indirect enzyme reactions, and the like. Commonly used detection assays include radioisotopes or non-radioisotope methods. These include Western blotting, overlay-analysis, Radioimmuno Assay (RIA) and Immune Radioimmunometric Assay (IRMA), Enzyme Immuno Assay (EIA), Enzyme Linked Immuno Sorbent Assay (ELISA), Fluorescent Immuno Assay (CIA) and Chemiluminoluminescent Immune Assay).

By using the pharmaceutical composition for preventing or treating ocular pain comprising the PGE2 synthesis inhibitor according to the present invention as an active ingredient, the ocular pain symptoms can be improved by selectively suppressing the expression level of PGE2, and furthermore, for the treatment and prevention of dry eye syndrome. It works. In addition, by using a kit for detecting the amount of PGE2, PGD2 and COX2 can easily diagnose the symptoms of eye pain in the clinic can be widely used to determine the condition of the patient as well as dry eye patients.

Figure 1 is a graph showing the relationship between the degree of PGE2 / PGD2 level contained in the tears of patients with eye pain symptoms and the symptoms of patients.

Figure 2 is a result showing the degree of eye discomfort after instilling a COX2 inhibitor in the mouse causing the eye pain.

Figure 3 is a result of measuring the mRNA level of TNF-alpha after instilling a COX2 inhibitor in the eye-induced mice.

Figure 4 is a result of measuring the mRNA level of IL-1 after instilling a COX2 inhibitor in the eye-induced mice.

Hereinafter, the present invention will be described in detail by the following examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples.

Example 1

Analysis of Tears in Eye Pain Patients

Twenty-three patients with non-Sjogren-type ocular pain and 17 normal eyes tears were collected using polyester fiber rods (TRANSORB® WICKS, FILTRONA, Richmond, VA) followed by nanoscale liquid chromatography. The level of prostaglandin in the tear was measured by a nano-liquid chromatography tandem mass spectrometry (LC-MS / MS) method (an Applied Biosystem / MDS Sciex 4000 Qtrap quadrupole mass spectrometer (AB / MDS Sciex). , Concord, Canada).

As a result, it was confirmed that the PGE2 level increased more than three times in the tears of the patients with ocular pain and that the PGD2 level decreased to 7% of the normal eye (Table 1).

Table 1 Dry Eye Patients (n = 46) Control group (n = 33) p value PGE2 (ng / ml) 136.25 ± 170.82 43.89 ± 41.83 0.003 ** PGD2 (ng / ml) 5.41 ± 11.00 72.15 ± 202.42 0.028 *

Example 2

Identifying eye pain symptoms according to PGE2 levels

In the patient group and the normal group showing ocular pain, the degree of symptom was checked by visual analogue scale before tears were collected. The visual pain scale was scaled from 0 to 10, with 0 being asymptomatic and 10 being unbearable pain or discomfort. It was statistically analyzed whether this was related to changes in prostaglandin levels.

As a result, it was confirmed that the value of the PGE2 / PGD2 ratio increases as the discomfort of the patient due to eye pain increases (FIG. 1).

Example 3

Mouse experiment caused eye pain

After B6 mice were exposed to dry eye chambers for 1 week in an environment causing eye pain, each substance known as a PGE synthesis inhibitor was divided into experimental groups and control groups. 5 μg / ml celecoxib (sigma) was added twice a day to the experimental group, and 0.1% hyaluronic acid (hyaluronic acid) was added to the control group.

After 1 week of instillation, corneal injury status of the experimental and control mice was measured using a standardized protocol. As a result, it was confirmed that the degree of corneal damage was significantly reduced in the experimental group instilled celecoxib (Fig. 2).

In addition, after one week of eye drops, the eyes of the experimental and control mice were extracted, and the levels of TNF-alpha and IL-1 mRNA on the eye surface were measured by real time RT-PCR. As a result, it was confirmed that in the experimental group instilled celecoxib, TNF-alpha, IL-1 mRNA levels are significantly reduced (Fig. 3, Fig. 4).

Example 4

PGE2 Synthesis Inhibitor Dosing Study in Patients with Ocular Pain

PGE2 synthesis inhibitors were administered to patients with ocular pain symptoms, and the number of eye blinks was reduced compared to the control group. PGE2 synthesis inhibitors used were 15-Deoxy-A12, 14-PGJ2, Exisulind, NS-398, Leukotnene C4, mk-886, Analogues of MK-886, MF63, Thienopyrrole, Naphthalene disulphonamide, Resveratrol, γ-hydroxybutenolide .

As a result, when the PGE synthesis inhibitor was applied, it was confirmed that the number of eye blinks was reduced compared to the control group by reducing eye discomfort (Table 2).

TABLE 2 Substances Used Blink (recovered / 5min) in treatment group (n = 10) Blink of control group (n = 10) (recovery / 5min) P value 15-Deoxy-A12, 14-PGJ2 11 25 0.03 * Exisulind 14 18 0.02 * NS-398 13 20 0.015 * Leukotnene C4 17 21 0.04 * mk-886 15 24 0.04 * Analoguesof MK-886 10 27 0.012 * MF63 9 24 0.02 * Thienopyrrole 13 23 0.005 * Naphthalene disulphonamide 16 20 0.004 * Resveratrol 17 19 0.04 * γ-hydroxybutenolide 18 22 0.037 *

Example 5

Selective COX2 Inhibitor Dosing Study in Patients with Ocular Pain

To determine whether selective COX2 inhibitors are effective in reducing ocular pain symptoms as compared to non-selective COX2 inhibitors, selective COX2 inhibitors, non-selective COX2 inhibitors and NSAIDs were administered. Selective COX2 inhibitors were applied to patients with ocular pain symptoms and the number of eye blinks was reduced compared to the control group (Diclofenac) with non-selective COX2 inhibitory properties. Selective COX2 inhibitors were structurally classified and used as Nimesulud, Celecoxib, Meloxicam, S-2474 (3,5-di-tert-buryl-4-hydroxybensylidene) and cis-Stilbenes as the representative substances. Ibuprofen was included as the NSAID with.

As a result, when the selective COX2 inhibitor was instilled, it was confirmed that the number of eye blinks was reduced compared to the control group by reducing eye discomfort (Table 3).

TABLE 3 Classification Substances Used Treatment group blinks (n = 3) Control blinks (n = 3) p value Classic NSAIDs with Selective COX-2 Inhibitor Properties Ibuprofen 17 25 0.03 Diaryl- or aryl-heteroaryl ethers and thioethers Nimesulud 16 22 0.04 Bisinal Diaryl Heterocycle Celecoxib 17 23 0.012 Structurally Modified classic NSAIDs and Other Compounds Meloxicam 20 26 0.04 Compounds with Antioxidant Components S-2474 15 27 0.004 1,2-diarylethylene derivative cis-Stilbenes 22 29 0.03

The specific parts of the present invention have been described in detail above, and it is apparent to those skilled in the art that such specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. something to do. Thus, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

By using the pharmaceutical composition for preventing or treating ocular pain comprising the PGE2 synthesis inhibitor according to the present invention as an active ingredient, the ocular pain symptoms can be improved by selectively suppressing the expression level of PGE2, and furthermore, for the treatment and prevention of dry eye syndrome. It is useful because it works.

SEQ ID NOs: 1 and 2 represent the PGE2 protein sequence and the gene sequence encoding the protein, respectively, and SEQ ID NOs: 3 and 4 represent the COX2 protein sequence and the gene sequence encoding the protein, respectively.

Claims (32)

A pharmaceutical composition for preventing or treating ocular pain, comprising the PGE2 synthesis inhibitor as an active ingredient. The method of claim 1, The PGE2 synthesis inhibitors are composed of 5-Deoxy-A12, 14-PGJ2, Exisulind, NS-398, Leukotnene C4, mk-886, Analogues of MK-886, MF63, Thienopyrrole, Naphthalene disulphonamide, Resveratrol and γ-hydroxybutenolide A pharmaceutical composition for preventing or treating ocular pain, which is selected. The method of claim 1, The pharmaceutical composition is a pharmaceutical composition for preventing or treating ocular pain, characterized in that to reduce the amount of PGE2 expression. The method of claim 1, The pharmaceutical composition is a suspension, powder, powder, granules, tablets, sustained release formulations, injections, ointments, eye drops, capsules, contact lens cleaners or contact lens lubricants, characterized in that the pharmaceutical composition for preventing or treating pain. The method of claim 1, The pharmaceutical composition is a pharmaceutical composition for preventing or treating eye pain, characterized in that the target for humans. The method of claim 1, The ocular pain is dry eye, inflammatory eye disease or eye pain due to the use of contact lenses, characterized in that the pharmaceutical composition for preventing or treating eye pain. Health functional food for the prevention or improvement of eye pain containing PGE2 synthesis inhibitor as an active ingredient. The method of claim 7, wherein The PGE2 synthesis inhibitors are composed of 5-Deoxy-A12, 14-PGJ2, Exisulind, NS-398, Leukotnene C4, mk-886, Analogues of MK-886, MF63, Thienopyrrole, Naphthalene disulphonamide, Resveratrol and γ-hydroxybutenolide Health functional food for preventing or improving eye pain, characterized in that selected. The method of claim 7, wherein The health functional food is a functional health food for preventing or improving eye pain, characterized in that to reduce the amount of expression of PGE2. The method of claim 7, wherein The health functional food is a capsule, tablets, granules, powder or a drink for health functional foods for preventing or improving eye pain, characterized in that the form. The method of claim 7, wherein The eye pain is dry eye, inflammatory eye disease or eye pain due to the use of contact lenses, eye pain prevention or improvement health functional food. (a) contacting a sample to be analyzed with a cell comprising the PGE2 protein represented by SEQ ID NO: 1; (b) measuring the amount or activity of the protein; And (c) determining that the sample is a substance that alleviates ocular pain when the amount or activity of the protein is determined to be modulated. The method of claim 12, The ocular pain is a dry eye, inflammatory eye disease or eye pain due to the use of contact lenses, the screening method of the eye pain relief agent characterized in that. (a) contacting a sample to be analyzed with a cell comprising a gene encoding a PGE2 protein represented by SEQ ID NO: 1; (b) measuring the expression level of the gene; And (c) determining that the sample is a substance for alleviating ocular pain when it is determined that the expression level of the gene is controlled to be reduced. The method of claim 14, The gene encoding the PGE2 protein is a screening method of ocular pain relief agent, characterized in that represented by SEQ ID NO: 2. The method of claim 14, Wherein the eye pain is dry eye, inflammatory eye disease or eye pain due to the use of contact lenses. (a) contacting a sample to be analyzed with a cell comprising a COX2 protein represented by SEQ ID NO: 3; (b) measuring the amount or activity of the protein; And (c) determining that the sample is a substance that alleviates ocular pain when the amount or activity of the protein is determined to be modulated. The method of claim 17, The ocular pain is a dry eye, inflammatory eye disease or eye pain due to the use of contact lenses, the screening method of the eye pain relief agent characterized in that. (a) contacting a sample to be analyzed with a cell comprising a gene encoding a COX2 protein represented by SEQ ID NO: 3; (b) measuring the expression level of the gene; And (c) determining that the sample is a substance for alleviating ocular pain when it is determined that the expression level of the gene is controlled to be reduced. The method of claim 19, The gene encoding the COX2 protein is a screening method of ocular pain relief agent, characterized in that represented by SEQ ID NO: 4. The method of claim 19, Wherein the eye pain is dry eye, inflammatory eye disease or eye pain due to the use of contact lenses. Pharmaceutical composition for preventing or treating ocular pain comprising a COX2 inhibitor as an active ingredient. (a) measuring the level of PGE2 represented by SEQ ID NO: 1 from a biological sample isolated from the patient; (b) providing information for diagnosing eye pain comprising comparing the level of PGE2 with that of a normal control sample. The method of claim 23, And measuring the level of PGD2 or COX2 and comparing the level with that of a normal control sample. The method according to claim 23 or 24, The levels of PGE2, PGD2 or COX2 are enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) Or measuring by LC-MS / MS. Kit for diagnosing or predicting eye pain comprising an antibody that specifically binds to a protein attached to PGE2. The method of claim 26, A kit for diagnosing or predicting eye pain further comprising an antibody that specifically binds to a protein attached to PGD2 or a protein attached to COX2. The method of claim 26 or 27, The attached protein is horseradish peroxidase (horseradish peroxidase), basic phosphatase (alkaline phosphatase) and β-galactosidase ocular pain diagnosis or prediction kit, characterized in that selected from the group consisting of. A method of preventing or treating ocular pain by administering a PGE2 synthesis inhibitor to a mammal. A method of preventing or treating ocular pain by administering a COX2 inhibitor to a mammal. Use of a PGE2 synthesis inhibitor to prevent or treat ocular pain. Use of a COX2 inhibitor to prevent or treat ocular pain.

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