KR102473451B1 - Composition for treatment and prevention of dry eye syndrome comprising aucubin - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of dry eye syndrome, comprising an extract of oyster capillaries.

Description

A pharmaceutical composition for preventing or treating dry eye syndrome containing an extract of thorax capricorn {Composition for treatment and prevention of dry eye syndrome comprising aucubin}

The present invention relates to a pharmaceutical composition for preventing or treating dry eye syndrome including hoeer cap.

Dry eye syndrome is not simply a lack of tears, but causes eye discomfort, visual acuity, and instability of the tear layer due to inflammation of the tears and the ocular surface (cornea and conjunctiva), causing damage to the ocular surface. There is a high risk of pain, irregular corneal surface, blurred and fluctuating vision, and corneal ulceration. However, these pathogenesis mechanisms have not yet been fully identified, but research results have been reported that inflammation plays an important role, such as infiltration of inflammatory cells, increased expression of immune activation molecules and adhesion molecules, Th1 and Th17 responses, and abnormal changes in apoptosis markers and chemokines. have. In general, intake of potassium and anthocyanin-rich foods is recommended for the treatment of dry eye syndrome, and fruits such as kale, kiwi, and apples are also highly recommended. Controlling therapies are also used. However, dry eye syndrome is a common disease that occurs in around 20% of adults in Korea. In particular, the number of patients with dry eye syndrome is continuously increasing due to global climate change, especially the temperature rise due to the El Niño phenomenon and environmental pollution, but special treatment or functional A situation where there is no food.

Sargassum horneri is a brown algae plant belonging to the family Sagassaceae and is an annual plant that forms colonies in the subtidal zone. , In Korea, it is used for food in some regions. Its main ingredients are rich in cultivated minerals such as polyphenols and fucoidan, and are known to have antiviral action, cholesterol lowering, and blood pressure suppression effects.

While researching a composition for preventing and treating dry eye syndrome, the present inventors confirmed that the extract of thorax molluscum contagiosum can treat dry eye syndrome by increasing tear secretion, preventing corneal dry damage, and inhibiting corneal inflammation in dry eye syndrome. The invention was completed.

The present invention has been made to solve the above problems, and the present inventors, while researching a composition for preventing and treating dry eye syndrome, found that the oxen cap extract increased tear secretion, prevented corneal dry damage, and inhibited corneal inflammation through It was confirmed that dry eye syndrome could be treated, and the present invention was completed.

An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of dry eye syndrome, comprising an extract of oleaginous capillaries.

Another object of the present invention is to provide a health functional food composition for preventing or improving dry eye syndrome, which contains an extract of thorax pterygoid.

Another object of the present invention is to provide a veterinary composition for preventing or treating dry eye syndrome in animals, containing an extract of thorax gnat.

Another object of the present invention is to provide a feed additive for preventing or improving dry eye syndrome containing an extract of genital warts.

The present invention can provide a pharmaceutical composition for the prevention or treatment of dry eye syndrome containing an extract of oleaginous capricorn.

The present invention can provide a health functional food composition for preventing or improving dry eye syndrome, which contains an extract of the black capsular capillaries.

The present invention can provide a veterinary composition for the prevention or treatment of dry eye syndrome containing an extract of the oyster cap.

The present invention can provide a feed additive for preventing or improving dry eye syndrome containing an extract of the black capsular capillaries.

The hoesaeng hat half may be a hot water extract.

The dry eye symptoms include anorexia, corneal dryness, Sjogren's syndrome, keratoconjunctivitis sicca, Steven-Johnson syndrome, eye-like blisters, dry eye syndrome after ophthalmic surgery, dry eye syndrome accompanied by allergic conjunctivitis, VDT (Visual Display Terminal) It may be any one selected from the group consisting of dry eye syndrome-like conditions including reduced tears in workers and reduced tears without any systemic symptoms caused by a dry room due to air conditioning.

The concentration of the thoracic capitis extract may be 1 to 1000 mg/kg.

The composition is any one selected from the group consisting of solutions, suspensions, syrups, emulsions, liposomes, powders, powders, granules, tablets, sustained release formulations, eye drops, capsules, contact lens cleaners and contact lens lubricants It may be a formulation of

The extract of the present invention has the effect of reducing cell death from dry stress in human corneal epithelial cells, increasing the secretion of tears in an animal model induced by dry eye syndrome, and restoring damage caused by dry cornea. have. Through this, there is an effect of treating, preventing, or improving dry eye syndrome of the hoesaeng capsular extract.

Figure 1 shows the result of confirming the cell viability after 24 hours after treatment with the extract of the spp.
FIG. 2 is a result of measuring the amount of tears after treatment with an extract of capsular capsularis in a dry eye syndrome animal model.
Figure 3 is a result of confirming the effect on corneal dryness damage in a dry eye animal model, (A) is a result showing the state of the corneal surface after treatment with the oleander capricorn extract, and (B) quantifies the result of (A) is a result

Hereinafter, the present invention will be described in detail.

Dry eye syndrome is not simply a lack of tears, but causes eye discomfort, visual acuity, and instability of the tear layer due to inflammation of the tears and the ocular surface (cornea and conjunctiva), causing damage to the ocular surface. There is a high risk of pain, irregular corneal surface, blurred and fluctuating vision, and corneal ulceration. However, these pathogenesis mechanisms have not yet been fully identified, but research results have been reported that inflammation plays an important role, such as infiltration of inflammatory cells, increased expression of immune activation molecules and adhesion molecules, Th1 and Th17 responses, and abnormal changes in apoptosis markers and chemokines. have. In addition, artificial tears, eye drops, and lacrimal punctures are blocked to control the amount of tears discharged. However, dry eye syndrome is a common disease that occurs in around 20% of adults in Korea. In particular, the number of patients with dry eye syndrome is continuously increasing due to global climate change, especially the temperature rise due to the El Niño phenomenon and environmental pollution, but special treatment or functional A situation where there is no food.

Accordingly, the inventors of the present invention, while researching a pharmaceutical composition for preventing and treating dry eye syndrome, confirmed that the oleaginous capricorn extract has preventive and therapeutic effects on dry eye syndrome, and completed the present invention. In an experiment in which drying stress was induced by exposing human corneal epithelial cells to the air for 25 minutes, the oxen cap extract had an effect of increasing cell viability (FIG. 1). It increased the amount of tears in an animal model of dry eye syndrome (FIG. 2) and reduced corneal damage due to dryness (FIG. 3).

The present invention provides a pharmaceutical composition for the prevention or treatment of dry eye syndrome, comprising an extract of oleaginous capricornus:

The hoesaeng hatban may be, for example, a hoesaeng hatban with the scientific name Sargassum horneri, but is not limited thereto.

The extraction site of the medicinal material is not particularly limited and all sites can be used.

The extraction solvent is not particularly limited, and for example, water or an organic solvent may be used, and the organic solvent includes methanol, ethanol, propanol, isopropanol, butanol, etc. Alcohol containing 1 to 4 carbon atoms, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane or cyclo Various solvents such as cyclohexane may be used alone or in combination, but are not limited thereto. Preferably, water can be used.

As an extraction method, any one of methods such as hot water extraction, cold brew extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression may be selected and used, preferably hot water extraction. In addition, the desired extract may be additionally subjected to a conventional fractionation process or may be purified using a conventional purification method. There is no limitation on the preparation method of the extract according to the present invention, and any known method may be used. As a specific example of hot water extraction, 3 to 20 times the weight of the medicinal material, specifically 10 times the amount of water added, and extracted at a temperature of 80 to 100 ° C., specifically 90 ° C. for 1 hour to 24 hours, specifically 8 hours It may be, but is not limited thereto.

The extract according to the invention may be subjected to processes such as filtration, concentration, and drying as necessary after the extraction. However, the conditions are not limited, and may be performed by a method known in the art, under commonly performed conditions.

The concentration of the thoracic capitis extract is not particularly limited, and may be preferably 1 to 1000 mg/kg, and more preferably 100 to 250 mg/kg.

The composition may be administered topically, transdermally, orally or parenterally, most preferably orally.

The composition is a formulation selected from the group consisting of solutions, suspensions, syrups, emulsions, liposomes, powders, powders, granules, tablets, sustained release formulations, eye drops, capsules, contact lens cleaners and contact lens lubricants can

The dry eye symptoms include anorexia, corneal dryness, Sjogren's syndrome, keratoconjunctivitis sicca, Steven-Johnson syndrome, eye-like blisters, dry eye syndrome after ophthalmic surgery, dry eye syndrome accompanied by allergic conjunctivitis, VDT (Visual Display Terminal) It may be any one selected from the group consisting of dry eye syndrome-like conditions including reduced tears in workers and reduced tears without any systemic symptoms caused by a dry room due to air conditioning.

When the composition is a pharmaceutical composition, it may include a pharmaceutically acceptable diluent or carrier. The diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and magnesium stearate, talc, or a combination thereof as a lubricant. The carrier may be an excipient, a disintegrant, a binder, a lubricant, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant may be calcium carboxymethyl cellulose, sodium starch glycolate, calcium monohydrogen phosphate anhydrous, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, or a combination thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof. The pharmaceutical composition may include the extract in an effective amount or as an active ingredient. The effective amount can be appropriately selected according to the individual. The severity of the disease, the patient's age, weight, health, sex, the patient's sensitivity to the drug, administration time, administration route and excretion rate, treatment period, factors including drugs used in combination or simultaneous use with the composition, and other medical fields It can be determined according to well-known factors.

The composition may include the extract in an effective amount or as an active ingredient, depending on its use. The effective amount can be appropriately selected according to the individual. The severity of the disease or condition, the subject's age, weight, health, sex, the subject's sensitivity to the extract, the administration time, administration route and excretion rate, administration period, factors including other compositions combined or used simultaneously with the composition, and other It may be determined according to factors well known in the physiological or medical fields.

The present invention can also provide a health functional food composition for preventing or improving dry eye syndrome, which includes the extract of the black capsular capillaries. The above description is substituted for the above description because the black capsular extract is the same as that used in the pharmaceutical composition.

The food composition according to the invention can be prepared in various forms according to conventional methods known in the art. General foods include, but are not limited to, beverages (including alcoholic beverages), fruits and their processed foods (e.g. canned fruits, bottled products, jams, marmalades, etc.), fish, meat and their processed foods (e.g. ham, sausages) Corned beef, etc.), breads and noodles (e.g. udon, buckwheat noodles, ramen, spagate, macaroni, etc.), fruit juice, various drinks, cookies, taffy, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine , Vegetable protein, retort food, frozen food, various seasonings (eg, soybean paste, soy sauce, sauce, etc.), etc., can be prepared by adding the extract of the present invention. In addition, nutritional supplements are not limited thereto, but may be prepared by adding the extract of the present invention to capsules, tablets, pills, etc. In addition, health functional foods are not limited thereto, but, for example, liquefied, granulated, encapsulated, and powdered so that the extract itself of the present invention can be prepared in the form of tea, juice, and drink so that it can be consumed (healthy beverage) It can be digested and consumed. In addition, in order to use the extract of the present invention in the form of a food additive, it can be prepared and used in the form of a powder or concentrate. In addition, it can be prepared in the form of a composition by mixing the capsular capitis extract of the present invention with a known active ingredient known to have an effect of preventing or improving dry eye syndrome.

The content of the extract of the black capsular capitis in the composition for health functional food may be appropriately determined depending on the purpose of use (prevention or improvement). In general, it may be included in 0.01 to 15% by weight of the total food weight, and when prepared as a beverage, it may be contained in a ratio of 0.02 to 10 g, preferably 0.3 to 1 g, based on 100 mL. The beverage may further include other components than the extract, and may further contain various flavoring agents or natural carbohydrates commonly used in beverages. Examples of the natural carbohydrate include common sugars such as monosaccharides (eg, glucose, fructose, etc.), disaccharides (eg, maltose, sucrose, etc.), polysaccharides (eg, dextrin, cyclodextrin, etc.) and xylitol, sorbitol, erythritol, etc. of sugar alcohols may be contained. In addition, natural flavoring agents (eg, thaumatin, stevia extract, etc.) and synthetic flavoring agents (eg, saccharin, aspartame, etc.) may be included as flavoring agents. The proportion of the natural carbohydrates may be generally about 1 to 20 g, preferably about 5 to 12 g per 100 mL of beverage.

The extract of the black capped cap of the present invention may be contained as an active ingredient in a food composition for preventing or improving dry eye syndrome, but the amount is not particularly limited to an effective amount to achieve the effect of preventing and improving dry eye syndrome, but the total weight of the total composition It is preferably 0.01 to 100% by weight relative to. The food composition of the present invention can be prepared by mixing the extract of the black oyster cap with other active ingredients known to be effective in compositions for preventing and improving dry eye syndrome.

In addition to the above, the health food of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, It may contain glycerin, alcohol or a carbonating agent and the like. In addition, the health food of the present invention may contain fruit flesh for producing natural fruit juice, fruit juice beverage, or vegetable beverage. These components may be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

The present invention can provide a veterinary composition for preventing or treating dry eye syndrome in animals, which includes an extract of capsular capitis.

The veterinary composition containing the extract of the thorax capsicum of the present invention may further include appropriate excipients and diluents according to conventional methods. Examples of excipients and diluents that may be included in the veterinary composition containing the extract of the oxen capsular capitis of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, and gelatin. , calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearyl alcohol, liquid paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben and mineral oil.

The veterinary composition containing the extract of thoracoccus japonica according to the present invention may further include a filler, an anti-agglomerating agent, a lubricant, a wetting agent, a spice, an emulsifier, a preservative, and the like. The veterinary composition according to the present invention is It can be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient, and the dosage form can be powders, granules, tablets, capsules, suspensions, emulsions, solutions, syrups, aerosols. , soft or hard gelatin capsules, suppositories, sterile solutions for injection, sterile external preparations, and the like.

The veterinary composition according to the present invention may include the extract in an effective amount or as an active ingredient, depending on its use. The effective amount can be appropriately selected according to the individual animal. The severity of the disease or condition, the subject's age, weight, health, sex, the subject's sensitivity to the extract, the administration time, administration route and excretion rate, administration period, factors including other compositions combined or used simultaneously with the composition, and other It may be determined according to factors well known in the physiological or veterinary field.

The animal may be a dog or cat, but is not limited thereto.

The present invention can provide a feed additive for preventing or improving dry eye syndrome containing an extract of capsular capitis.

The feed additive may be in the form of a highly concentrated liquid, powder, or granular form containing the extract of the black oyster cap. The feed additive of the present invention includes organic acids such as citric acid, fumaric acid, adipic acid, lactic acid, and malic acid, phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, polyphosphate (polyphosphate), polyphenol, catechin, alpha - At least one selected from natural antioxidants such as tocopherol, rosemary extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, and phytic acid may be further included.

The animal feed additives containing the extract of the present invention and the feed containing the same are amino acids, inorganic salts, vitamins, antibiotics, antibacterial substances, antioxidants, antifungal enzymes, digestion and absorption enhancers, growth promoters, and diseases as auxiliary ingredients. It can be used together with substances such as prophylaxis.

The feed additive may be administered to the animal alone or in combination with other feed additives in an edible carrier. In addition, the feed additives can be easily administered as a top dressing or directly mixed with animal feed or separately from feed, as a separate oral formulation, by injection or transdermally, or in combination with other ingredients. Typically, a single daily dose or divided daily doses may be used, as is well known in the art. When the feed additives are administered separately from the animal feed, dosage forms of the extracts can be prepared as immediate release or sustained release formulations by combining them with non-toxic pharmaceutically acceptable edible carriers, as is well known in the art. Such edible carriers can be solid or liquid, for example corn starch, lactose, sucrose, soybean flakes, peanut oil, olive oil, sesame oil and propylene glycol. When a solid carrier is used, the dosage form of the extract may be tablets, capsules, powders, troches or sugar-containing tablets, or top dressing in a microdispersible form. When a liquid carrier is used, it may be a soft gelatin capsule, or a dosage form of a syrup or liquid suspension, emulsion or solution. In addition, the dosage form may contain adjuvants such as preservatives, stabilizers, wetting or emulsifying agents, solution accelerators, and the like. In addition, the animal feed containing the black capsular gnat extract as a feed additive may be any protein-containing organic flour commonly used to meet the dietary needs of animals. These protein-containing grains usually consist mainly of corn, soybean flour or corn/soybean flour mixes. The feed additive may be used by adding it to the animal feed by dipping, spraying or mixing. The veterinary composition or feed additive of the present invention can be applied to the diet of companion animals.

The present invention can also provide a functional feed composition for preventing or improving dry eye syndrome, which includes an extract of the black capsular capillaries.

If the composition is a functional feed composition, it may be formulated into a conventional feed formulation known in the art. The composition for feed may be prepared in general formulations such as powders, granules, tablets, pills, capsules, suspensions, emulsions, syrups, precipitates, liquids, extracts, etc., or may be prepared in any feed form. For the formulation of the feed, veterinary nutritionally acceptable additives may be used, and any additive known to be usable in the art may be used for the preparation of the formulation to be prepared.

The content of the extract in the functional feed composition may be appropriately determined according to the purpose of use (prevention or improvement). In general, it may be included in 0.01 to 20% by weight of the total feed weight.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for explaining the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

EXAMPLE 1. Preparation of the extract of oyster capsular capitis

In order to prepare the extract of the kkeosaeng moss, it was purchased from the Haenam Fisheries Cooperative (Haenam, Jeollanam-do, Korea) and used. It was washed three times with purified water to remove salt, dried naturally to a moisture content of 10% or less, sealed until extraction, and stored at room temperature until extraction. 1000 parts by weight of water was added to 100 parts by weight of the hoesaeng cap, and then hot water extraction was performed at 100 ° C. for 3 hours to obtain an extract, which was filtered through a 50 μm filter to obtain a filtrate. The filtrate was concentrated under reduced pressure at 50±10° C. and then freeze-dried for about 72 hours until the moisture content was less than 5%. (Yield 20±5%)

Example 2. Inhibition of cell damage by drying stress in corneal epithelial cells

Corneal epithelial cells (PCS-700-010, American Type Culture Collection, Manassas, VA, USA) were cultured in corneal epithelial cell basal medium containing growth supplements according to the manufacturer's (American Type Culture Collection, Manassas, VA, USA) instructions. cultured. Cell viability was measured using an MTS assay kit (Promega Corporation). Cells (1 x 10 ⁴ ) were grown in a 96-well plate, and 0.1 to 100 μg/mL of oxen hat extract (SHE) After treatment, the pretreatment was performed by culturing for 24 hours. After that, the medium was removed and exposed to air for 25 minutes to induce drying stress. After that, the degree of cell damage was analyzed by MTS. The result of the MTS analysis was micro Absorbance was measured using a plate reader (Tecan Group Ltd., Mannedorf, Switzerland), and as a result, the oxen capus extract increased cell viability under drying stress in a dose-dependent manner (FIG. 1).

Example 3. Evaluation of Tear Secretion Improvement Functionality of Molar Capricorn Extract Using Dry Eye Syndrome Model Animals

3.1 Experimental animals and design

6-week-old SD rats were purchased from Orient Co., Ltd. and acclimatized for one week. One week later, the exorbital lacrimal gland was surgically removed under deep anesthesia to induce dry eye syndrome. After 1 week, a phenol-red thread tear test strip (FCI Opthalmics Zone Quick, Japan) is brought into contact with the ocular surface at the outer end of the eyelid, and after 30 seconds, the length of the test strip's color change due to tears is measured. did Among them, only the subjects whose tear secretion was markedly reduced compared to the non-surgical group were selected and the drug efficacy test was conducted. After the groups were separated, the extracts of the black oyster cap (SHE) were formulated to be administered at concentrations of 50 mg/kg, 100 mg/kg, and 200 mg/kg once a day, and were orally administered for 1 week. Breeding of laboratory animals and all experimental procedures using laboratory animals were approved by the Animal Experimentation Ethics Committee of Chonbuk National University and were carried out in accordance with the regulations.

3.2 Analysis of tear volume and corneal dryness

Tear secretion was measured by measuring the length of the color change of the test strip by the tears after 30 seconds after contacting the phenol-red thread tear test strip (FCI Opthalmics Zone Quick, Japan) with the ocular surface at the outer end of the eyelid. . The dry eye model showed a lower amount of tears than the normal group, but the amount of tear secretion increased in a concentration-dependent manner after the treatment of the black cap. (Fig. 2). Corneal dry damage is measured by shining a ring type light illuminator on the cornea and taking a picture of the reflected shape, and then taking a picture of the degree of corneal dry damage caused by the circular light. 1 point: corneal damage in 1/4, 2 points: corneal damage in 2/4, 3 points: corneal damage in 3/4, 4 points total cornea damage). In the dry eye model, the cornea was damaged due to dryness and diffusely reflected light, showing an irregular circular shape of light. (Fig. 3A). In addition, it was confirmed that the corneal dry damage score was high in the dry eye syndrome group, but low in the concentration-dependent manner in the corneal dryness group (FIG. 3B).

Claims (9)

A pharmaceutical composition for the prevention or treatment of dry eye syndrome, comprising an extract of thorax capella. The pharmaceutical composition for the prevention or treatment of dry eye syndrome according to claim 1, wherein the extract of capsular capitis is a water or organic solvent extract. The pharmaceutical composition for preventing or treating dry eye syndrome according to claim 1, wherein the composition is administered topically, transdermally, orally or parenterally. The pharmaceutical composition for the prevention or treatment of dry eye syndrome according to claim 1, wherein the extract of the oleaginous capricorn is contained in a concentration of 1 mg/kg to 1000 mg/kg. 2. The method of claim 1, wherein the composition consists of solutions, suspensions, syrups, emulsions, liposomes, powders, powders, granules, tablets, sustained release formulations, eye drops, capsules, contact lens cleaners and contact lens lubricants. Any one formulation selected from the group, a pharmaceutical composition for the prevention or treatment of dry eye syndrome.
The method of claim 1, wherein the dry eye syndrome is anorexia, corneal dryness, Sjogren's syndrome, keratoconjunctivitis sicca, Steven-Johnson syndrome, eye-like blister, dry eye syndrome after ophthalmic surgery, dry eye syndrome with allergic conjunctivitis, VDT (visual terminal) (Visual Display Terminal)) of dry eye syndrome, which is any one selected from the group consisting of dry eye disease-like conditions including reduced tears of workers and reduced tears without any systemic symptoms caused by dry rooms due to air conditioners. A pharmaceutical composition for prevention or treatment.
A health functional food composition for preventing or improving dry eye syndrome, comprising an extract of black oyster cap.
A veterinary composition for preventing or treating xerophthalmia in animals, comprising an extract of thoracic capitis.
A feed additive for preventing or improving dry eye syndrome, comprising an extract of oxen caps.

Images