CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a National Phase of International Application No. PCT/KR2017/014957 filed Dec. 18, 2017, currently pending, which designated the U.S. and that International Application was published under PCT Article 21(2) in English. This application also includes a claim of priority under 35 U.S.C. § 119(a) and § 365(b) to Korean patent application No. KR 10-2016-0173715 filed Dec. 19, 2016, and Korean patent application No. KR 10-2017-0174313 filed Dec. 18, 2017 the entirety of which is hereby incorporated by reference.

TECHNICAL FIELD

The present invention relates to a composition for preventing and treating a Bruch's membrane dysfunction-associated disease, which contains a sea cucumber extract as an active ingredient, and more particularly, to a composition for preventing and treating a Bruch's membrane dysfunction-associated disease, which contains a sea cucumber extract and has effects of regenerating the Bruch's membrane of an eye and improving a transport function.

BACKGROUND ART

Sea cucumber is a generic term for sea cucumbers that are echinoderms from the class Holothuroidea, and the best health food called ginseng in the sea since a large amount of saponins is contained as an active ingredient like ginseng. Sea cucumber is a medicine for compensating for body fluids from ancient times in the East including China, and has been known as a drug that has excellent effects on diabetes and asthma, and can be used to regain energy when a person loses energy and collapses due to a lot of sweating caused by a rise in temperature during summer. In addition, when a part of the body of sea cucumber is cut, the cutting site returns to its original state within three months, and even when the organs are removed, there is an amazing resilience in that a new organ is generated within a month, and therefore, in oriental and folk medicines, it has been known that sea cucumber enhances the phagocytic ability of human mononuclear cells and macrophages, such that it exhibits a full immune function and is effective in wound treatment.

Sea cucumbers are used for child development-promoting food, tonic food for the elderly, post-recovery food, anemia-preventing food for pregnant women, or food for stimulating bowel movements and have received attention as diet food since they contain less fat and sugar. However, there is no study of the effect of a sea cucumber extract on improvement in eye function.

Photoreceptor cells are light detecting cells present in the retina and transport information to the brain to recognize an object in the visual process. Photoreceptor cells are the most metabolically active cells in the body and therefore require efficient delivery of nutrients and removal of waste products. Since these cells operate in an environment rich in essential fatty acids, light, and a high concentration of oxygen, the cells undergo considerable free radical-induced damage. In this case, retinal pigment epithelium (RPE) cells are used to continuously regenerate the outer segments of the damaged photoreceptor cells.

Photoreceptor cells and RPE cells receive nutrients through choroidal blood circulation. When nutrients provided from blood are secreted from choroidal capillaries, before reaching the RPE cells and photoreceptor cells, first, they should pass through an extracellular matrix called the Bruch's membrane. Small-sized nutrients such as glucose, oxygen, amino acids, etc. pass through the Bruch's membrane by simple passive diffusion, and vitamins, trace metals and lipids are bound to carrier proteins, and then separated from the RPE cells through the Bruch's membrane. In contrast, waste generated from photoreceptor cells and the RPE cells is removed from the choroid through the Bruch's membrane. Since the waste is generally toxic, it can damage the Bruch's membrane, and initiate inflammation. Therefore, an efficient material transport ability of the Bruch's membrane is essential for the maintenance of normal vision and survival of photoreceptor cells (FIG. 1).

Due to aging, the thickness of the Bruch's membrane is increased two- to three-fold, and thus the diffusion gradients for exchange of nutrients and waste are reduced, making it difficult to diffuse materials into the Bruch's membrane. Accordingly, lipids, proteo-lipid complexes and waste discarded from RPE cells are deposited on the membrane, the cross-linking of collagen increases, and the amount of denatured collagen increases. In addition, not only amounts of glycosylation-induced glycation products of proteins and lipids (AGE; advanced protein glycation end-products, ALE; advanced lipid glycation end-products) are increased (Handa et al. 1999), but also the deposition of damaged or polymerized protein complexes is also increased, eventually interfering with the transport ability of a membrane (Holz et al. 1994), and adversely affecting the delivery of nutrients and the removal of waste (FIG. 2).

In the case of age-related macular degeneration (AMD), for which aging is a major risk factor, age-related changes become much more serious, the reduced transport ability of the Bruch's membrane leads to the death of RPE cells and photoreceptor cells and thus blindness (FIG. 3).

Clinically, in the aging of the Bruch's membrane in the elderly, diminished scotopic thresholds caused by inefficient regeneration of vitamin A have been reported (Steinmetz et al. 1993; Owsley et al. 2001). Currently, in some countries, administration of vitamin A is prescribed with metals and anti-oxidants, but there are two problems in this strategy. First, only specific nutrients are added, and thus other essential nutrients are still deficient, and secondly, when a metal is added to the Bruch's membrane decreased in transport function, a concentration of the metal in the Bruch's membrane is increased and subsequently deposited in the membrane, resulting in further increasing the damage thereby. In addition, according to the Age-Related Eye Disease Study (AREDS), which is a US macular degeneration clinical test in progress for over 10 years, the effects of compositions consisting of vitamins and mineral additives have not been demonstrated yet (Kassof et al. 2001).

An ideal solution is to facilitate the transport ability of the Bruch's membrane, allowing all of the nutrients that are present in plasma to be provided.

As a result of intensive efforts to develop a treatment method capable of addressing the fundamental reason for age-related eye dysfunction including AMD, the inventors of this application found effects of a sea cucumber extract improvement in the transport ability of the Bruch's membrane and regeneration of the Bruch's membrane by a sea cucumber extract, and confirmed that the sea cucumber extract is able to be used as a composition for preventing and treating a Bruch's membrane dysfunction-associated disease. Therefore, the present invention was completed.

REFERENCES

[1] Birkedal-Hansen H, Moore W G, Bodden M K, Windsor L J, Birkendal-Hansen B, DeCarlo A, Engler J A. (1993) Matrix metalloproteinases: a review. Crit. Rev. Oral Biol. Med. 4:197-250.[2] Handa J T, Verzijl N, Matsunaga H, Aotaki-Keen A, Lutty G A, to Koppele J M, Miyata T and Hjelmeland L M. Increase in the advanced glycation end-product pentosidine in Bruch's membrane with age. Invest. Ophthalmol. Vis. Sci. 1999; 40: 775-779.[3] Holz F G; Sheraidah G S, Pauleikhoff D and Bird A C. Analysis of lipid deposits extracted from human macular and peripheral Bruch's membrane. Arch. Ophthalmol. 1994; 112: 402-406.[4] Hussain A A, Lee Y, Zhang J J, Marshall J. (2011) Disturbed matrix metalloproteinase activity of Bruch's membrane in age-related macular degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 52:4459-66.[5] Hussain A A, Starita C, Hodgetts A, Marshall J. (2010) Macromolecular characteristics of ageing human Bruch's membrane: implications for age-related macular degeneration (AMD). Exp. Eye Res. 90:703-710.[6] Hussain A A, Lee Y, Marshall J. (2010) High molecular weight gelatinase species of human Bruch's membrane: compositional analyses and age-related changes. Invest. Ophthalmol. Vis. Sci. 51:2363-71.[7] Hussain A A, Starita C, and Marshall J. (2004) Chapter IV. Transport characteristics of ageing human Bruch's membrane: Implications for AMD. In: Focus on Macular Degeneration Research, (Editor O. R. Ioseliani). Pages 59-113. Nova Science Publishers, Inc. New York.[8] Hussain A A, Rowe L, Marshall J. (2002) Age-related alterations in the diffusional transport of amino acids across the human Bruch's-choroid complex. Journal of the Optical Society of America, A, Optics, Image Science, & 19(1): 166-72.[9] Karwatowski W S S, Jefferies T E, Duance V C, Albon J, Bailey A J & Easty D L. Preparation of Bruch's membrane and analysis of the age-related changes in the structural collagens. (1995) Brit. J. Ophthalmol. 79: 944-952.[10] Kassof A, Kassoff J, Buehler J, et al., A randomized, placebo-controlled, clinical trial of high dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report No. 8. Arch Ophthalmol. 2001; 119:1417-36.[11] Kumar A, El-Osta A, Hussain A A, Marshall J. (2010) Increased sequestration of matrix metalloproteinases in ageing human Bruch's membrane: implications for ECM turnover. Invest. Ophthalmol. Vis. Sci. 51:2664-70.[12] Moore D J and Clover G M. The effect of age on the macromolecular permeability of human Bruch's membrane. Invest. Ophthalmol. Vis. Sci. 2001; 42: 2970-2975.[13] Moore D J, Hussain A A, Marshall J. (1995). Age-related variation in the hydraulic conductivity of Bruch's membrane. Invest. Ophthalmol. Vis. Sci. 36(7): 1290-7.[14] Owsley C, Jackson G R, White M, Feist R and Edwards D. Delays in rod mediated dark adaptation in early age-related maculopathy. Ophthalmol. 2001; 108: 1196-1202.[15] Owsley C, McGwin Jackson G R, Heinburger D C, Piyathilake C J, Klein R, White M F, Kallies K. Effect of short term, high-dose retinol on dark adaptation in age and age-related maculopathy. Invest. Ophthalmol. Vis. Sci. 2006. 47(4):1310-8.[16] Ramratten R S, van der Schaft T L, Mooy C M, de Bruijn W C, Mulder P G H and de Jong P T V M. Morphometric analysis of Bruch's membrane, the choriocapillaris and the choroid in ageing. Invest. Ophthalmol. Vis. Sci. 1994; 35: 2857-2864.[17] Starita C, Hussain A A, Pagliarini S, Marshall J. (1996) Hydrodynamics of ageing Bruch's membrane: implications for macular disease. Exp. Eye Res. 62(5): 565-72.[18] Steinmetz R L, Haimovici R, Jubb C, Fitzke F W, Bird A. Symptomatic abnormalities of dark adaptation in patients with age-related Bruch's membrane change. Br. J. Ophthalmol. 1993; 77:549-554.[19] Hussain A A, Lee Y (2016) unpublished data[20] Lee Y, Hussain A A, Seok J, Kim S, Marshall J. (2015). Modulating the Transport Characteristics of Bruch's Membrane With Steroidal Glycosides and its Relevance to Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 56(13): 8403-18.

DISCLOSURE

Technical Problem

The present invention is directed to providing a pharmaceutical composition for preventing, delaying and treating a Bruch's membrane dysfunction-associated disease, which contains an extract or fraction of sea cucumber as an active ingredient.

The present invention is also directed to providing a health functional food composition for preventing, delaying and treating a Bruch's membrane dysfunction-associated disease, which contains an extract or fraction of sea cucumber as an active ingredient.

The present invention is also directed to providing a pharmaceutical composition for preventing, delaying and treating a Bruch's membrane dysfunction-associated disease, which contains Frondoside A, an isomer thereof, a hydrate thereof or a salt thereof as an active ingredient.

The present invention is also directed to providing a health functional food composition for preventing, delaying and treating a Bruch's membrane dysfunction-associated disease, which contains Frondoside A, an isomer thereof, a hydrate thereof or a salt thereof as an active ingredient.

Technical Solution

To attain the above-described objects, the present invention provides a pharmaceutical composition for preventing, delaying and treating a Bruch's membrane dysfunction-associated disease, which contains an extract or fraction of sea cucumber as an active ingredient.

The term “sea cucumber” used herein refers to a marine invertebrate belonging to the Class Holothuroidea and the Phylum Echinodermata, and includesPsolus squamatus, Lipotrapeza japonica, Sclerodactyla multipes, Cucumaria, Plesiocolochirus inornatus, etc., which belong to the Order Dendrochirotacea,Apostichopus japonicus, Holothuria monacaria, Holothuria argus, Holothuria manacaria, etc., which belong to the Order Aspidochirotida, Synaptidae,Polycheira rufescens, etc., which belong to the Order Apodida,Paracaudina chilensis, Molpadia oolitica, etc., which belong to the Order Molpadida, but the present invention is not limited thereto. The sea cucumber is recommended for use as tonics for promoting strength, medicines for a pregnant woman and an infirm woman, a health food for hypertension, arteriosclerosis, a diabetic patient and an obese patient, but no effect on age-related eye diseases has been known.

The term “extract” used herein includes an extract obtained by extracting sea cucumber, a dried product obtained by drying sea cucumber, a diluent or concentrate of the extract, a dried product obtained by drying the extract, a partially purified component or purified component of the extract, or a mixture thereof, a liquid extract, and all forms of extracts that can be formed using the liquid extract itself. The extract or fraction of the present invention may be preferably used in the form of a liquid after extraction.

In the sea cucumber extract of the present invention, the method of extracting the sea cucumber is not particularly limited, and thus an extraction method conventionally used in the art may be used. Non-limiting examples of the extraction methods may include hot water extraction, ultrasonic extraction, filtration, reflux extraction, etc., which may be used independently, or in combination of two or more thereof.

In the present invention, a type of an extraction solvent used to extract the sea cucumber is not particularly limited, and thus any solvent known in the art may be used. Non-limiting examples of the extraction solvents may include water, an alcohol, and a mixed solvent thereof, and as a solvent, preferably, a C1 to C4 alcohol, more preferably, a C1 to C2 low alcohol, and even more preferably, an 80% ethanol aqueous solution may be used, but the present invention is not limited thereto. The sea cucumber extract of the present invention is preferably water or an ethanol extract.

In the present invention, when the extraction of the sea cucumber is performed by hot water extraction, the sea cucumber is preferably extracted 1 to 5 times, and more preferably 3 times, but the present invention is not limited thereto. The extraction solvent may be added at 0.1- to 100-fold, and preferably 0.3- to 5-fold the dry sea cucumber weight. An extraction temperature is preferably 20 to 130° C., but the present invention is not limited thereto. In addition, an extraction time is preferably 30 minutes to 48 hours, but the present invention is not limited thereto.

In a method of preparing the sea cucumber extract, preferably, vacuum evaporation is performed using a vacuum concentrator or a rotary vacuum evaporator, but the present invention is not limited thereto. In addition, drying is performed by decompression drying, vacuum drying, boiling drying, spray drying, or freeze drying, but the present invention is not limited thereto.

Although a method of preparing the dried product of sea cucumber may be natural drying, hot-air drying or freeze drying, any method known in the art for removing moisture from the sea cucumber is used without limitation.

In the method of extracting or drying sea cucumber according to the present invention, the outer coat and the internal organs of the sea cucumber may be entirely or separately extracted or dried, and the extract or dried product of the outer coat or the internal organs may be used individually or in combination thereof.

According to an exemplary embodiment of the present invention, an extract may be obtained by preparing a sea cucumber powder by grinding dried sea cucumber, adding 70% ethanol as an extraction solvent to the sea cucumber powder to perform extraction for about 3 to 6 hours, and removing the ethanol under a vacuum condition.

The term “fraction” used herein refers to a product obtained by performing fractionation to isolate a specific component or specific component group from a mixture including various components.

A fractionation method for obtaining the fraction in the present invention is not particularly limited, and thus a method conventionally used in the art may be used. A non-limiting example of the fractionation method may include a method of obtaining a fraction from the extract by treating an extract obtained by extracting sea cucumber with a predetermined solvent.

In the present invention, a type of a fractionation solvent used to obtain the fraction is not particularly limited, and thus any solvent known in the art may be used. Non-limiting examples of the fractionation solvents may include polar solvents such as water, an alcohol, etc.; and non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane, etc. These may be used alone, or in combination of two or more thereof. Among the fractionation solvents, a C1 to C4 alcohol is preferably used.

Since an active ingredient of the present invention improves the transport function of the Bruch's membrane, it is effective in preventing the occurrence of a Bruch's membrane dysfunction-associated disease, delaying the progression of the disease, or treating the disease.

The active ingredient of the present invention may improve the hydraulic conductivity of the Bruch's membrane, improve the material diffusion function of the Bruch's membrane, or remove proteins or lipids bound to or trapped in the Bruch's membrane, thereby improving the transport function.

The active ingredient of the present invention is effective in preventing the occurrence of a Bruch's membrane dysfunction-associated disease, delaying the progression of the diseases or treating the disease by regenerating the Bruch's membrane and improving the functions of the Bruch's membrane.

The active ingredient of the present invention may regenerate the Bruch's membrane and improve the functions thereof by removing a high molecular weight (HMW) complex or a lipid component, which is bound to or deposited on the Bruch's membrane.

In addition, the active ingredient of the present invention may regenerate the Bruch's membrane and improve the functions thereof by secreting pro-MMP2, pro-MMP9, active MMP2 and active MMP9 from the matrix of the Bruch's membrane.

In addition, the active ingredient of the present invention may regenerate the Bruch's membrane and improve the functions thereof by activating the secretion of active MMPs from RPE cells.

As described above, the sea cucumber extract composition of the present invention helps to decompose materials which are polymerized in the Bruch's membrane, thereby aging the Bruch's membrane and allowing the functions thereof to be lost, and to supply nutrients to the eyes and discharge waste by secreting nutrients such as proteins or lipids trapped in or bound to the matrix of the Bruch's membrane and waste. In addition, as the sea cucumber extract composition of the present invention allows the recovery of the function of an enzyme by secreting MMPs of the Bruch's membrane, it is involved in regenerating the functions of the Bruch's membrane, and increases the hydraulic conductivity and material diffusion of the eyes, resulting in prevention of retinal aging, and an effect of preventing, delaying and treating the age-related loss of retinal functions by regenerating the retinal functions.

The term “prevention” or “delay” used herein refers to all actions involved in inhibiting or delaying the occurrence of a disease occurring due to Bruch's membrane dysfunction by administering the composition of the present invention to a subject.

The term “treatment” used herein refers to all actions involved in alleviating or beneficially changing symptoms of a disease occurring by Bruch's membrane dysfunction by administering the composition of the present invention to a subject.

The term “improvement” used herein refer to all actions involved in at least reducing parameters related to conditions being treated, for example, the severity of symptoms.

In the pharmaceutical composition of the present invention, the sea cucumber extract or a fraction thereof is preferably contained at 0.1 to 99.99 wt %, more preferably, 10 to 99.99 wt %, and even more preferably, 50 to 99.99 wt % based on the total weight of the pharmaceutical composition. Within the above range, there is an advantage of being more suitable for achieving the objects of the present invention due to sufficient effects of the sea cucumber extract or a fraction thereof on improvement of the transport function of the Bruch's membrane, regeneration of the Bruch's membrane, and improvement of the functions of the Bruch's membrane.

The pharmaceutical composition of the present invention may contain the sea cucumber extract or a fraction thereof as an active ingredient, and further contain a pharmaceutically acceptable carrier.

In the present invention, the “pharmaceutically acceptable” means conventionally being used in the pharmaceutical field without irritating an organism when the composition is administered thereto and inhibiting the biological activity and characteristics of the administered compound.

The pharmaceutical composition of the present invention may be formulated with the carrier, and thus used in food, medicines, feed supplements, drinking water supplements, etc. In the present invention, a type of the carrier is not particularly limited, and any carrier conventionally used in the art is able to be used. Non-limiting examples of the carriers may include saline, distilled water, Ringer's solution, buffered saline, an albumin injection solution, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, maltodextrin, glycerol, ethanol, etc. These carriers may be used alone or in combination of two or more thereof.

In addition, the pharmaceutical composition of the present invention may be used by adding a pharmaceutically acceptable additive such as an excipient, a diluent, an antioxidant, a buffer or a bacteriostatic agent, if needed, and further adding a filler, a thickening agent, a wetting agent, a disintegrant, a dispersant, a surfactant, a binder or a lubricant.

The pharmaceutical composition of the present invention may be formulated in various forms suitable for oral or parenteral administration. Non-limiting examples of preparations for oral administration may include troches, lozenges, tablets, water-soluble suspensions, oil-soluble suspensions, formulated powder, granules, emulsions, hard capsules, soft capsules, syrups or elixirs.

To formulate the pharmaceutical composition of the present invention for oral administration, the composition may include a binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin; an excipient such as dicalcium phosphate; a disintegrating agent such as corn starch or sweet potato starch; or a lubricant such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax, a sweetening agent, a flavoring agent, a syrup agent, etc.

Further, other than the above-described materials, as a capsuling agent, a liquid carrier such as fat oil may be further added.

Non-limiting examples of the parenteral preparations may include injections, suppositories, respiratory inhalation powder, an aerosol for spray, an ointment, an applicable powder, oil, a cream, etc.

To formulate the pharmaceutical composition of the present invention for parenteral administration, a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, a freeze-dried preparation, or an external preparation may be used, and as the non-aqueous solvent or suspending agent, propylene glycol, polyethylene glycol, a vegetable oil such as olive oil, or an injectable ester such as ethyl oleate may be used.

In addition, more specifically, when the pharmaceutical composition of the present invention is formulated in the form of an injection fluid, the composition of the present invention may be mixed with a stabilizer or buffer in water, thereby preparing a solution or suspension, and the solution or suspension may be formulated in a unit dosage form such as an ampoule or vial. In addition, when the pharmaceutical composition of the present invention is formulated as an aerosol, it may be mixed with additives such as a propellant, etc. to disperse a water-diffused concentrate or wet powder.

In addition, when the pharmaceutical composition of the present invention is formulated in the form of an ointment or cream, an animal oil, a vegetable oil, wax, paraffin, starch, tragacanth, a cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as a carrier.

A pharmaceutically effective amount or effective dose of the pharmaceutical composition of the present invention may vary according to a formulation method, an administration method, an administration time and/or administration route of the pharmaceutical composition, and specifically, may vary according to various factors and similar factors well known in the medical field such as the type and degree of a reaction to be accomplished by administrating the pharmaceutical composition, the type, age, body weight and general health condition of a subject for administration, the symptoms or severity of a disease, sex, diet, excretion, components of a drug or other compositions used together for a corresponding subject at the same or different time, etc. Those of ordinary skill in the art may easily determine and prescribe an amount or dose effective for the desired treatment.

The dose of the pharmaceutical composition of the present invention for a more preferable effect is preferably 0.01 to 1,000 mg/kg, and more preferably, 1 to 500 mg/kg per day. The pharmaceutical composition of the present invention may be daily administered once, or divided into several doses. Therefore, the dose may not limit the scope of the present invention in any way.

The administration route and method of the pharmaceutical composition of the present invention may be independent of each other. The method is not particularly limited, and thus any administration route and method may be used as long as the pharmaceutical composition can reach a desired relevant site. The pharmaceutical composition may be orally or parenterally administered.

As parenteral administration, for example, intravenous administration, intraperitoneal administration, intravenous administration, transdermal administration or subcutaneous administration, application or spraying of the composition onto a diseased site or inhalation may be used, but the present invention is not limited thereto.

The pharmaceutical composition of the present invention is preferably administered orally or injected.

The composition of the present invention may further include Frondoside A to prevent and delay a Bruch's membrane dysfunction-associated disease, and increase a therapeutic effect thereof.

The “Frondoside A” used herein is a saponin compound represented by the following formula, and is known to be included in the sea cucumber of the present invention. Its CAS No. is 127367-76-4 (anhydrous), and its chemical formula is C60H96O29SNa. In the present invention, it is confirmed that Frondoside A is involved in improving the hydraulic conductivity of the Bruch's membrane, improving the transport function of the Bruch's membrane through MMP and lipid secretion, regenerating the Bruch's membrane, and improving the functions thereof, and through this, a novel use of Frondoside A for preventing, delaying, treating and improving a Bruch's membrane dysfunction-associated disease was identified.



The composition of the present invention may further include one or more compositions selected from the group consisting of amino acids, antioxidant materials, minerals, metallic materials, lutein, astaxanthin and zeaxanthin to prevent and delay a Bruch's membrane dysfunction-associated disease, and increase a therapeutic effect thereof.

In the present invention, the Bruch's membrane dysfunction-associated disease may be AMD, Sorsby's fundus dystrophy, Malattia Levintanese (ML), Stargardt disease, Best's vitelliform retinal dystrophy or Doyne's honeycomb retinal dystrophy (DHRD), but the present invention is not limited thereto.

In addition, the present invention provides a health functional food composition for preventing, delaying and treating a Bruch's membrane dysfunction-associated disease, which contains the sea cucumber extract as an active ingredient.

In the health functional food composition of the present invention, the sea cucumber extract or a fraction thereof, and an efficacy thereof is the same as described above in connection with the pharmaceutical composition of the present invention.

When the health functional food composition of the present invention is used as a food additive, it may be suitably used as is or in combination with a different food or food component according to a conventional method.

A type of the food is not particularly limited, and includes all types of food in a general sense. Non-limiting examples of food to which the material is added may include meat, sausage, bread, chocolate, candy, snacks, confectioneries, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes.

When the health functional food composition of the present invention is a beverage composition, like a general beverage, various flavors or natural carbohydrates may be contained as additional components. Non-limiting examples of the natural carbohydrates may include monosaccharides such as glucose, fructose, etc.; disaccharides such as maltose, sucrose, etc.; natural sweetening agents such as dextrin, cyclodextrin, etc.; and synthetic sweeteners such as saccharin and aspartame. The proportion of the additional component added may be suitably determined by one of ordinary skill in the art.

Other than these, the health functional food composition of the present invention may contain a variety of nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and a salt thereof, alginic acid and a salt thereof, an organic acid, a protective colloid thickening agent, a pH adjuster, a stabilizer, a preservative, glycerin, an alcohol, or a carbonating agent used in carbonated beverages. Other than these, the health functional food composition of the present invention may contain fruit pulp for preparing natural fruit juices, fruit drinks or vegetable drinks. These components may be used independently or in combination of two or more thereof. The proportions of these additives may also be suitably selected by one of ordinary skill in the art.

In addition, the present invention provides a pharmaceutical composition for preventing, delaying and treating/improving a Bruch's membrane dysfunction-associated disease, which includes Frondoside A, an isomer thereof, a hydrate thereof or a salt thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for preventing, delaying and treating a Bruch's membrane dysfunction-associated disease, which includes Frondoside A, an isomer thereof, a hydrate thereof or a salt thereof as an active ingredient.

Advantageous Effects

A composition according to the present invention is effective in improving the transport function of the Bruch's membrane, and delaying or restoring the aging of eyes by stimulating the regeneration of the Bruch's membrane, and can also have excellent efficacy in preventing and treating a disease such as AMD occurring due to age-related Bruch's membrane dysfunction, Sorsby's fundus dystrophy, ML, Stargardt disease, Best's vitelliform retinal dystrophy or DHRD.

