KR102275250B1 - Composition for preventing and treating dry eye syndrome comprising selenium and propolis as active ingredients - Google Patents

Abstract

The present invention relates to a composition for preventing and treating dry eye syndrome comprising selenium and propolis as active ingredients, and a method for treating dry eye syndrome using the composition.

Description

Composition for preventing and treating dry eye syndrome, comprising selenium and propolis as active ingredients {Omitted}

The present invention relates to a composition for preventing and treating dry eye syndrome comprising selenium and propolis as active ingredients, and a method for treating dry eye syndrome using the composition.

Dry eye syndrome is a disease in which the eye becomes dry due to a decrease in tear secretion when the eye is exposed to the external environment or surgical damage such as surgery is induced, such as after ophthalmic surgery such as LASIK or LASEK, or when working with the eyes for a long time. . Dry eye syndrome causes various symptoms such as decreased visual acuity, pain, and ocular discomfort as the ocular surface becomes dry. Secondary, due to the increase in inflammation on the ocular surface, inflammatory cell infiltration and inflammatory cytokines and chemokines of immune cells due to inflammation It causes secondary ophthalmic disease by abnormal increase. In the case of chronic dry eye syndrome, corneal discomfort increases and it is often difficult to lead a normal daily life. Although the exact cause of dry eye syndrome is not known, it is known that the tear layer production decreases due to cell degeneration caused by damage to corneal cells or prolonged stimulation.

The treatment of dry eye syndrome consists of ingredients that make up the tear layer, such as RESTASIS® (Cyclosporin A), DIQUAS® (Diquafosol), and Hyalein® (Sodium Hyaluronate), or substances that promote the formation of the tear layer, such as mucin, and substances that relieve corneal inflammation. Although eye drops containing it are commercially available, there is a disadvantage in that the burning sensation in the eyes and the feeling of the eye drops are not good. In particular, a treatment for dry eye disease through oral administration is not commercially available, and foods rich in omega-3, anthocyanin, and potassium help to alleviate dry eye syndrome and are strongly recommended to be consumed. However, dry eye disease through oral administration is not commercially available. A therapeutic agent has not yet been developed.

Selenium was known as a toxic substance before its chemical symbol Se had an atomic number of 34, but is currently recognized as an essential trace element in the body where an appropriate amount of selenium acts as an enzyme cofactor such as an antioxidant enzyme in the living body. In particular, as it is known for its antioxidant ability, which is stronger than vitamin E, it is being used in various health functional foods as an anti-aging nutrient. Until recently, selenium's value as a health functional food is increasing as not only its antioxidant ability but also its immune function enhancement, cardiovascular disease alleviation, and anticancer activity are known.

Propolis is a substance produced by bees and has strong antibacterial and sterilizing power, so it is a natural antibacterial agent that is applied to the crevices of the beehive to prevent the intrusion of external pathogens or viruses. Since propolis contains various minerals and flavonoids, it is known as a substance with bactericidal, antioxidant and anticancer properties.

Accordingly, the present inventors have been studying oral food-derived materials that can compensate for the shortcomings of dry eye eye drops and increase the therapeutic effect as an expert in ophthalmic diseases for many years. Among various materials, when selenium and propolis were administered orally, the tear secretion increased and the symptoms of dry eye syndrome were alleviated for the first time. Selenium and propolis were administered alone or together orally, or together with omega-3 or omega-6. The present invention was completed by confirming that the amount of tear secretion further increased when taken.

An object of the present invention is to provide a pharmaceutical composition for the treatment of dry eye syndrome containing selenium and propolis as active ingredients. The pharmaceutical composition may be an artificial tear eye drop containing selenium and propolis, may be an oral health functional food, or an oral pharmaceutical composition, to provide a method of administering it in a pharmaceutically useful amount using the same.

The present inventors have been studying oral food-derived materials that can compensate for the shortcomings of artificial tears eye drops and increase the therapeutic effect, while selenium and propolis increase the proliferation of goblet cells in the eye that produce mucin, thereby increasing the amount of tear production. was confirmed to be excellent, and it was confirmed that a composition containing selenium and propolis as active ingredients could be used as a treatment for dry eye syndrome or as a therapeutic adjuvant. The technology for treating dry eye syndrome using selenium or propolis is not known at all until now, and was discovered for the first time by the present inventors. Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating dry eye syndrome using selenium or propolis as an active ingredient.

The present invention also provides a food, food additive, beverage, beverage additive, ophthalmic ophthalmic solution and cosmetic composition for the purpose of preventing and treating dry eye disease, characterized in that the composition comprises the selenium and propolis as active ingredients.

It may be a composition containing omega-6, omega-3, and isoflavones in order to increase the prevention and treatment effect of dry eye syndrome of the composition containing selenium and propolis as active ingredients.

Dry eye syndrome used in the present invention is corneal dryness, dry corneal conjunctivitis, dry eye after ophthalmic surgery, dry eye due to inflammation of the lacrimal gland, and dry eye caused by abnormal tear evaporation due to abnormal eyelid function. It may be one selected from .

The pharmaceutical composition used in the present invention means one prepared for the prevention and treatment of diseases, and can be prepared and used in various formulations according to each conventional method. For example, it can be formulated in the form of tablets, granules, capsules, suspensions, emulsions, syrups, etc., and can be formulated as external preparations, suppositories, and injections. More specifically, as a formulation suitable for eye drop administration, it may be formulated into eye drops, creams, ointments, and gels.

The dosage of the pharmaceutical composition of the present invention can be selected by those skilled in the art in consideration of various aspects depending on the purpose of use, the presence or absence of disease, the age, weight, sex, and amount of the active ingredient used. For example, the composition may be administered orally at 0.1 ng - 100 mg/kg per adult or 0.001%-10% (w/v) included in eye drops, specifically 1ng-10mg/kg oral It can be administered or administered as an external solution at 0.01%-1%. The frequency of administration is not particularly limited, but it can be administered once a day or divided into several doses, but the dosage or frequency of administration does not limit the scope of the present invention.

The pharmaceutical composition of the present invention may be administered by routes such as eye drop administration, oral administration, intraperitoneal administration, intravenous administration, subcutaneous administration, rectal administration, etc., according to the purpose, and specifically, intraocular administration or oral administration. have.

The pharmaceutical composition comprising selenium and propolis as active ingredients of the present invention increases the proliferation of goblet cells in the eye, where selenium and propolis produce mucin, to compensate for the shortcomings of the artificial tear eye drops and to enhance the therapeutic effect, thereby increasing the amount of tear As a principle of increasing dry eye syndrome, it can be utilized in the development of various pharmaceutical compositions for the prevention and treatment or treatment assistance.

The dry eye syndrome prevention and treatment effect of the pharmaceutical composition comprising selenium and propolis as active ingredients of the present invention will be described in more detail through examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1) Selenium treatment effect on dry eye syndrome

To create an experimental psoriasis eye mouse model, 2 mg/ml of scopolamine was administered to the mice three times a day to induce dry eye syndrome, and selenium 0, 0.1, 0.5, and 1 uM were administered three times a day, respectively, to the mice. One drop at a time was instilled. The number of each administration was 5 animals per group. After administration for 2 weeks, the amount of tear secretion and goblet cells were measured.

1) Measurement of tear secretion

The amount of tear secretion was measured by microscopy and converted into volume by contacting Phenol-red impregnated cotton threads with the conjunctival sac of the outer ocular side of the mouse for 20 seconds. the results are as follow.

Vehicle 0uM 0.1 uM 0.5 uM 1uM tear secretion
(Tear Volume) 0.055±0.006 0.056±0.007 0.065±0.004 0.068±0.008 0.069±0.006

2) Assess the density of goblet cells

The mouse eye tissue was fixed in 4% paraformaldehyde, put in paraffin, and then a tissue section was made and PAS staining was performed on the tissue section. For each section, the density of goblet cells in the conjunctiva was calculated using a high-magnification microscope and image-analysis software.

The result is as follows.

Vehicle 0uM 0.1 uM 0.5 uM 1uM goblet cell
density 3.8±0.7 3.6±0.6 8.3±0.8 8.9±0.7 7.3±0.8

From the above results, it can be seen that when selenium is administered by eye drop, it is effective in treating dry eye syndrome by proliferating goblet cells in the cornea that secrete mucin to increase tear secretion.

Example 2) Treatment effect of dry eye syndrome of propolis

A mouse model of psoriasis was made in the same manner as in Example 1, and 0, 0.01 , 0.05, 0.1 uM of propolis was administered by eye drop, respectively, 3 times a day, respectively. The number of each administered animal is the same as in Example 1.

1) Measurement of Tear Volume

It was measured in the same way as in Example 1) and converted into volume. The result is as follows.

Vehicle 0uM 0.01uM 0.05uM 0.1 uM tear secretion
(Tear Volume) 0.053±0.005 0.050±0.008 0.069±0.005 0.070±0.007 0.060±0.007

2) Evaluation of goblet cell density

The density per unit volume was measured by PAS staining in the same manner as in Example 1. The result is as follows.

Vehicle 0uM 0.01uM 0.05uM 0.1 uM goblet cell
density 3.6±0.4 3.7±0.8 9.3±0.6 10.9±0.5 6.3±0.7

Through the above results, it can be seen that when propolis is instilled, it is effective in treating dry eye syndrome by increasing the amount of tear secretion by proliferating goblet cells in the cornea that secrete mucin.

Example 3) Effect of co-administration of selenium and propolis

In order to examine whether the effect increases when selenium and propolis, which have been confirmed for efficacy in Examples 1 and 2, are administered together, 1 drop of selenium 0.1uM, propolis 0.01uM, selenium 0.1uM + propolis 0.01uM, 3 times a day, respectively A comparative experiment in which each instillation was administered was conducted.

1) Measurement of tear secretion

Vehicle 0 selenium propolis selenium + propolis tear secretion
(Tear Volume) 0.050±0.005 0.052±0.008 0.065±0.005 0.062±0.006 0.075±0.007

2) Goblet cell density evaluation

Vehicle 0 selenium propolis selenium + propolis goblet cell
density 3.2±0.4 3.4±0.8 7.8±0.7 8.8±0.6 10.8±0.8

Through the above results, it can be seen that when selenium and propolis are administered in combination, the goblet cell proliferation is further promoted and the tear secretion is increased, thereby further increasing the efficacy of treating dry eye syndrome when selenium and propolis are administered in combination.

Claims (5)

Selenium and propolis as active ingredients, but 0.005 - 10% (w/v) by the total volume of the composition, wherein the composition increases the amount of goblet cells that promote mucin production, characterized in that it increases the amount of tear secretion pharmaceutical composition. delete The pharmaceutical composition according to claim 1, wherein the composition is administered orally or by eye drops. delete delete