WO2018147663A1 - Composition comprising composite extract from ginseng/red ginseng and sea cucumber as effective ingredient for preventing or treating bruch's membrane hypofunction-related disease - Google Patents

Abstract

The present invention relates to a composition comprising a sea cucumber and ginseng/red ginseng composite extract as an effective ingredient for preventing or treating a Bruch's membrane hypofunction-related disease and, more particularly, to a composition for preventing, treating, or alleviating a Bruch's membrane hypofunction-related disease, the composition comprising a sea cucumber and ginseng/red ginseng composite extract which has the effect of regenerating the Bruch's membrane of the eye and improving the transport function of the Bruch's membrane. A composite composition according to the present invention improves the transport function of the Bruch's membrane and eliminates lipids accumulated on the membrane to promote the regeneration of the Bruch's membrane, thereby showing the effect of delaying or reversing the senescence process of the eye. Further, the composition is highly preventive or therapeutic of various diseases attributed to a decrease in the function of the Bruch's membrane with age, including age-related macular degeneration (AMD) and can solve the problem associated with the eye health maintenance of ordinary persons and with the transport reduction, resulting from senescence, of vitamins, metals, and anti-oxidative materials.

Description

A composition for preventing or treating diseases related to Bruch's membrane deterioration, comprising ginseng / red ginseng and sea cucumber complex extract

The present invention relates to a composition for preventing or treating diseases related to Brueck's membrane deterioration, comprising ginseng / red ginseng and sea cucumber complex extract as an active ingredient, and more specifically, having an effect of regenerating the Bruk's membrane of the eye and improving transportation function. It relates to a composition for preventing, treating or ameliorating diseases associated with decreased Bruch's membrane function including ginseng / red ginseng and sea cucumber complex extract.

Ginseng is one of the traditional medicines used in the treatment of various diseases in Asian countries such as China, Korea and Japan. Ginseng saponin (ginsenoside), the main active ingredient of these ginseng, has various physiological activities such as anti-aging, anti-inflammatory, antioxidant activity in the central nervous system and cardiovascular and immune system, antidiabetic activity and anti-tumor activity. Known. To date, more than 30 species of ginsenosides have been identified and isolated from ginseng saponins. Glycosides, which include aglycone with a dammarane skeleton, have been identified as protopanaxadiol. Ginsenosides Rb1, Rb2, Rc, Rd belonging to the system saponins, and ginsenosides Re and Rg1 belonging to the protopanaxatriol system saponins occupy most of them.

The fresh ginseng of ginseng, white ginseng, dried and red ginseng once steamed. Peel the white ginseng and dry it for 1 ~ 2 days in the sun, and straightly dry it without bending it. It is called ginseng, and it is called grain ginseng or semi-grain ginseng depending on the degree of bending. Also, the root of the ginseng is dried and called samsam.

Sea cucumber is a general term of sea cucumbers belonging to the equatorial animal sea cucumber river, and it is the best supplement product called sea ginseng because it contains a large amount of medicinal ingredients such as saponin. Sea cucumber is a medicine that has been used for a long time in China and the East. It has excellent effects on diabetes, asthma, etc., and it is a medicine that can regain energy when you lose energy and collapse due to sweating due to temperature increase in summer. Known. In addition, sea cucumbers have a remarkable resilience effect that when the part of the body is cut, the cut site returns to its original state in three months, and new intestines are formed in one month even if the intestines are removed. Enhance phagocytosis of the phagocytes to boost the immune function and is known to be effective in the treatment of wounds.

Eye cells are light-sensitive cells in the retina that transmit information to the brain during visual processes, allowing objects to be recognized. Eye cells are the most active part of our body's metabolism, and effective nutrient delivery and waste removal are essential. Due to the nature of an environment rich in essential fatty acids, light and high levels of oxygen, much of the damage is caused by free radicals. In this case, retinal pigment epithelium (RPE) can be used to continuously regenerate the outer segments of damaged cells.

Eye cells and RPE are supplied with nutrients through the choroid blood circulation. If nutrients from the blood are secreted from the capillaries of the choroid, they must first pass through the extracellular matrix Bruch's membrane before reaching the RPE and the cell. Nutrients such as small glucose, oxygen, and amino acids pass through the Bruch's membrane with simple passive diffusion, and vitamins, trace metals, and lipids bind to the carrier protein and then pass through the Bruch's membrane to the RPE. Are separated. In contrast, waste products from the cells and RPE pass through the Bruch's membrane and are removed from the choroid. Most waste products are toxic and can potentially damage the Brueck's membrane and trigger inflammatory reactions. Therefore, the efficient mass transport ability of the Bruch's membrane can be seen as a prerequisite for maintaining normal visual acuity and survival of visual cells (FIG. 1).

Aging increases the thickness of the Brueck membrane by two to three times, reducing the diffusion gradients in which nutrients and waste are exchanged, making it difficult to spread the material in the Brueck membrane. This results in deposition of lipids and proteo-lipid complexes and waste products discarded in RPE on membranes, increased cross-linking of collagen and increased amounts of denatured collagen. In addition, glycosylation increases protein and lipid glycosides (AGE; advanced protein glycation end-products, ALE; advanced lipid glycation end-products) (Handa et al. 1999), and damaged or polymerized proteins. Deposition of complexes also increases. In addition, the thiols in the free state are reduced because thiol groups exposed to normal or denatured proteins due to aging are trapped in the membrane as they form dimers or polymers through oxidation. All these changes result in disruption of the membrane's transport capacity and adversely affect nutrient delivery and waste removal (Holz et al. 1994) (Fig. 2).

These changes due to aging are much more rapid and severe in the case of age-related macular degeneration (AMD), in which aging is the main cause of disease, and the transport capacity of the Brueck membrane is reduced. As a result, RPE and visual cells are blinded by death (Fig. 3).

Clinically, the aging of the Bruk's membrane in the elderly population has been reported to reduce scotopic thresholds due to insufficient vitamin A regeneration (Steinmetz et al. 1993; Owsley et al. 2001), currently in some countries Is prescribed by adding metal and antioxidants to vitamin A. There are two problems with this method. The first is that only certain nutrients are added, so that other essential nutrients are still in scarce condition. The second is that when metal is added to the Brueck's membrane, which has reduced transport, It continues to be deposited on the membrane, and the damage is inevitably even greater. In addition, the age-related eye disease study (ARDS), a US-related macular degeneration study that has been conducted for more than 10 years, has not yet demonstrated the effectiveness of a composition consisting of vitamin and mineral additives (Kassof et al. 2001).

The ideal solution to macular degeneration and vision damage due to aging is to facilitate the transport of Brueck's membrane, so that all the necessary nutrients in the plasma are supplied.

The inventors of the present application have made diligent efforts to develop a therapeutic method that can solve the root cause of eye deterioration due to aging, including age-related macular degeneration. The present invention was completed by finding out that the regenerating effect is excellent and confirming that it can be used as a composition for the prevention or treatment of diseases caused by a decrease in the function of Bruk's membrane.

Reference Literature

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An object of the present invention is a complex extract of ginseng and sea cucumber or fractions thereof; Or it provides a pharmaceutical composition for the prevention, delay or treatment of Bruch's membrane function-related diseases including a complex extract of red ginseng and sea cucumber or fractions thereof as an active ingredient.

Another object of the present invention is a complex extract of ginseng and sea cucumber or fractions thereof; Or to provide a health functional food composition for the prevention, delay or improvement of Bruch's membrane (function) related to the functional degradation related to red ginseng and sea cucumber complex extract or fractions thereof as an active ingredient.

Another object of the present invention is a complex extract of ginseng and sea cucumber or fractions thereof; Or to provide a health functional food composition for improving eye health comprising a red ginseng and sea cucumber complex extract or fractions thereof as an active ingredient.

Another object of the present invention is a complex extract of red ginseng and sea cucumber or fractions thereof; Or it provides a method for preventing, delaying or treating a disease related to Brueck's membrane deterioration comprising administering to a subject a composition comprising a complex extract of ginseng and sea cucumber or a fraction thereof as an active ingredient.

The present invention is to solve the above problems, a complex extract of ginseng and sea cucumber or fractions thereof; Or it provides a pharmaceutical composition for the prevention, delay or treatment of Bruch's membrane function-related diseases, including a complex extract of red ginseng and sea cucumber or fractions thereof as an active ingredient.

The term "ginseng" used in the present invention is Korean ginseng ( Panax ginseng ), hoegisam ( P. quiquefolius ), Jeonchisam ( P. notoginseng ), bamboo shoots ( P. japonicus ), trifolium ginseng ( P. trifolium ), Himalayan ginseng ( P. pseudoginseng ), vietnamese ginseng ( P. vietnamensis ), and American ginseng ( P. quinquefolium ). In particular, the term "red ginseng" of the present invention is prepared by heating the ginseng through steam or sun-dried, preferably steam, more preferably steamed ginseng at 98 ~ 100 ℃, dried ginseng around 60 ℃ do. The present invention is described as being applied to ginseng or red ginseng extract, but can be applied to all ginseng processed in various forms, such as ginseng, rice ginseng, white ginseng, taegeuk ginseng, black ginseng, purified ginseng, enzyme-treated ginseng, fermented ginseng and fermented red ginseng It is not limited thereto.

The term "sea cucumber" used in the present invention refers to marine invertebrates belonging to Phylum Echinodermata Class Holothuroidea, scale sea cucumber, Hwamun sea cucumber, multifoot ring sea cucumber, Orthodox sea cucumbers, Monakari sea cucumbers, Snake-eye black sea cucumbers, Sea cucumbers, etc. belonging to the Order Aspidochirotida, etc. ) May include, but is not limited to, white sea cucumbers, ginseng sea cucumbers, and the like. The sea cucumber is recommended as a health food for high blood pressure, arteriosclerosis, diabetic and obese patients, but it is recommended for the use of rejuvenation and tonics, pregnant women and women with weak physical condition. There is no bar. The term "extract" used in the present invention is an extract obtained by the extraction process of ginseng / red ginseng or sea cucumber, dried product obtained by drying the ginseng, red ginseng or sea cucumber, dilution or concentrate of the extract, dried product obtained by drying the extract, And extracts of all formulations that can be formed using the extract itself and the extract, such as modifiers and purified products of the extract, or mixtures thereof. The extract or fraction of the present invention may preferably be used in liquid form after extraction.

In the complex extract of ginseng / red ginseng and sea ginseng of the present invention, the method of extracting the ginseng / red ginseng and sea ginseng is not particularly limited, and may be extracted according to methods commonly used in the art. Non-limiting examples of the extraction method, hot water extraction method, ultrasonic extraction method, filtration method, reflux extraction method and the like, these may be carried out alone or in combination of two or more methods.

In the present invention, the type of extraction solvent used to extract the ginseng / red ginseng and sea ginseng is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent include water, alcohols or mixed solvents thereof, and when using alcohol as the solvent, preferably C1 to C4 alcohol, more preferably C1 to C2 lower alcohol More preferably, 80% ethanol aqueous solution may be used, but is not limited thereto. The sea cucumber extract of the present invention may preferably be water or ethanol extract.

In the present invention, when extracting the ginseng / red ginseng and sea cucumber by the hot water extraction method, it is preferable to extract once to five times, more preferably three times to extract repeatedly, but is not limited thereto. The extraction solvent may be added 0.1 to 100 times the weight of the dried ginseng / red ginseng and sea cucumber, preferably 0.3 to 5 times. Extraction temperature is preferably 20 ℃ to 130 ℃ but is not limited thereto. In addition, the extraction time is preferably 30 minutes to 48 hours, but is not limited thereto.

In the method for preparing the ginseng / red ginseng and sea cucumber extract of the present invention, the vacuum concentration is preferably a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, the drying is preferably natural drying, hot air drying, freeze drying, vacuum drying, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited to any method known in the art to remove moisture. .

In the sea cucumber extraction or drying method of the present invention, the skin and gut of the sea cucumber can be extracted or dried as a whole, and the skin and gut of the sea cucumber can be separated or dried separately, respectively, and the skin and gut extract or dried It may be used or may be mixed.

According to one embodiment of the present invention, after washing and increasing ginseng, red ginseng was prepared by first drying at 60-70 ° C. for 12-20 hours, and then sun-dried, hot water over 4 times using water as a solvent. After extraction, the resultant was filtered, cooled, centrifuged, purified, and concentrated in vacuo to obtain an extract.

According to another specific embodiment of the present invention, the dried sea cucumber is ground to prepare a sea cucumber powder, 70% ethanol is added thereto as an extraction solvent, and extracted for about 3 to 6 hours, and ethanol is removed in a vacuum state. To obtain an extract.

As used herein, the term "fraction" refers to the result obtained by performing fractionation to separate a specific component or a specific group of components from a mixture comprising several different components.

In the present invention, the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art. Non-limiting examples of the fractionation method is a method of obtaining a fraction from the extract by treating the extract obtained by extracting ginseng / red ginseng and sea cucumbers with a predetermined solvent.

The kind of the fractionation solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractionation solvents include polar solvents such as water and alcohols; Nonpolar solvents, such as hexane, ethyl acetate, chloroform, dichloromethane, etc. are mentioned. These may be used alone or in combination of two or more thereof. In the case of using alcohol in the fractionation solvent, alcohols of C1 to C4 may be preferably used.

The active ingredient of the present invention has an effect of preventing the onset of the disease, delaying the progress of the disease, or treating the disease related to the decrease of the Bruk's membrane function by improving the transport function of the Bruk's membrane.

The active ingredient of the present invention is transported by improving the hydraulic conductivity of the Brueck membrane, improving the diffusion function of the Brueck membrane, or removing proteins or lipids bound or trapped in the Brueck membrane. You can improve the function.

The active ingredient of the present invention can prevent the onset of the disease, delay the progression of the disease, or treat the disease by which the Bruch membrane is reduced by improving the Brux membrane function.

The active ingredient of the present invention can regenerate the Brueck membrane and improve the Brueck membrane function by removing the high molecular weight complex (HMW) or lipid component bound or deposited on the Brueck membrane.

In addition, the active ingredient of the present invention can regenerate the Brooke membrane and improve the Brooke membrane function by secreting pro-MMP2, pro-MMP9, active MMP2 and active MMP9 from the matrix of the Brooke membrane.

In addition, the active ingredient of the present invention can regenerate the Bruch's membrane by activating the active MMP secretion from retinal epithelial cells (RPE), and improve the Bruch's membrane function.

As described above, the complex extract of ginseng / red ginseng and sea cucumber of the present invention is polymerized on the Bruch membrane to degrade the substances that degrade the Bruch membrane, and decomposes the substances, which are trapped in the matrix of the Brux membrane, or nutrients such as proteins or lipids bound together. Secretions and waste products help nourish the eyes and release waste products. In addition, it is possible to restore the function of enzymes by releasing the MMP of the Bruch's membrane to restore the function of the enzyme.In addition, it increases the repair conductivity and the diffusion of substances in the eye, thereby preventing the retina's aging and preventing the retina's function. Regeneration is effective in preventing, delaying or treating the loss of retinal function due to aging.

As used herein, the term "prevention" or "delay" refers to any action that inhibits or delays the onset of a disease resulting from a decreased function of the Bruch's membrane by administering the composition of the invention to a subject.

As used herein, the term "treatment" refers to any action by which the composition of the present invention is administered to a subject so that the symptoms of a disease resulting from a decreased function of the Bruch's membrane improve or benefit.

As used herein, the term " improvement " means any action that at least reduces the parameters associated with the condition being treated, such as the extent of symptoms.

In the pharmaceutical composition of the present invention, the complex extract of ginseng / red ginseng and sea cucumber or fractions thereof may be contained in an amount of preferably 0.1 wt% to 99.99 wt% based on the total weight of the pharmaceutical composition, More preferably, it may be contained in 10% by weight to 99.99% by weight, and more preferably 50% by weight to 99.99% by weight. Within this range, the effect of improving the transport function of the Brux membrane, the Brux membrane regeneration and the Brux membrane function improvement according to the complex extract or fractions thereof of the ginseng / red ginseng and sea cucumber is fully exhibited to achieve the object of the present invention There is an advantage.

The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier, in addition to containing the complex extract or fractions thereof of the ginseng / red ginseng and sea cucumber as an active ingredient.

In the present invention, the "pharmaceutically acceptable" means that it is commonly used in the pharmaceutical field that does not impede the biological activity and properties of the compound to be administered without stimulating the organism upon administration thereof.

The pharmaceutical composition of the present invention may be formulated with the carrier, and may be utilized as food, medicine, feed additives, drinking water additives, and the like. In the present invention, the type of the carrier is not particularly limited and any carrier can be used as long as it is commonly used in the art. Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, maltodextrin, glycerol, ethanol, and the like. Can be. These 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 other pharmaceutically acceptable additives, such as excipients, diluents, antioxidants, buffers or bacteriostatic agents, if necessary, fillers, extenders, wetting agents, disintegrants, dispersants, interfaces Active agents, binders, lubricants, and the like may be additionally added and used.

The pharmaceutical compositions of the present invention can be formulated and used in a variety of formulations suitable for oral or parenteral administration. Non-limiting examples of the formulation for oral administration include troches, lozenges, tablets, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups or elixirs, and the like. Can be mentioned.

In order to formulate the pharmaceutical composition for oral administration, a binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose (Cellulose) or gelatin (Gelatin) and the like; Excipients such as Dicalcium phosphate and the like; Disintegrants such as corn starch or sweet potato starch; Lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate, or polyethylene glycol wax can be used, and sweeteners, fragrances, and syrups can also be used. Can be.

Furthermore, in the case of a capsule, a liquid carrier such as fatty oil may be additionally used in addition to the above-mentioned materials.

Non-limiting examples of the parenteral preparations include injection liquids, suppositories, respiratory inhalation powders, spray aerosols, ointments, application powders, oils, creams, and the like.

In order to formulate the pharmaceutical composition for parenteral administration, a sterile aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a freeze-dried preparation, an external preparation, and the like may be used. The non-aqueous solvent and the suspension may be propylene glycol, Polyethyleneglycol, vegetable oils such as olive oil, injectable esters such as ethyloleate and the like can be used.

Further, more specifically, when the pharmaceutical composition of the present invention is formulated into an injection solution, the composition of the present invention is mixed with water with a stabilizer or buffer to prepare a solution or suspension, which is then used as an ampoule or vial. It can be formulated for unit administration of. In addition, when the pharmaceutical composition of the present invention is formulated with an aerosol, a propellant or the like may be combined with the additive to disperse the dispersed concentrate or the wet powder.

In addition, when the pharmaceutical composition of the present invention is formulated into an ointment, a cream, etc., animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, oxidation It can be formulated using zinc etc. as a carrier.

A pharmaceutically effective amount, effective dosage of the pharmaceutical composition of the present invention may vary depending on the method of formulation, the mode of administration, the time of administration and / or route of administration, and the like, to achieve by administering the pharmaceutical composition. The type and extent of the response, type of subject, age, weight, general state of health, condition or extent of the disease, sex, diet, excretion, drug used concurrently or simultaneously with the individual And various similar factors well known in the medical arts, and those skilled in the art can readily determine and prescribe a dosage effective for the desired treatment.

The dosage for the more preferred effect of the pharmaceutical composition of the present invention may be preferably 0.01 mg / kg to 1,000 mg / kg, more preferably 1 mg / kg to 500 mg / kg per day. Administration of the pharmaceutical composition of the present invention may be administered once a day, may be divided into several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The route of administration and mode of administration of the pharmaceutical composition of the present invention may be independent of each other, and are not particularly limited in the way, and any route of administration and administration as long as the pharmaceutical composition can reach the desired site of interest. You can follow the way. The pharmaceutical composition may be administered by oral or parenteral administration.

As the parenteral administration method, for example, intravenous administration, intraperitoneal administration, intramuscular administration, transdermal administration or subcutaneous administration may be used, and the method of applying, spraying or inhaling the composition to a diseased site may also be used. May be, but is not limited to these.

The pharmaceutical composition of the present invention may be preferably administered orally or transdermally.

The composition of the present invention is one selected from the group consisting of amino acids, antioxidants, vitamins, minerals, metals, lutein, astaxanthin, zeaxanthin and bilberry extract in order to enhance the prevention, delay or treatment effect of Bruch's membrane-related diseases It may further comprise the above composition. More specifically, the vitamin or mineral may be vitamin C, vitamin E, beta carotene, zinc oxide, and cupric oxide, which are effective for improving eye function, but are not limited thereto.

In the present invention, the Bruch's membrane deterioration-related diseases include age-related macular degeneration (AMD), Sorsby's fundus dystrophy, ML (Malattia Levintanese), Stargardt disease (Stargardt disease), Best yolk-shaped macular dystrophy (Best's) vitelliform retinal dystrophy) or Doyne's honeycomb retinal dystrophy (DHRD), but is not limited thereto.

In addition, the present invention is a complex extract of the ginseng and sea cucumber or fractions thereof; Or it provides a health functional food composition for the prevention, delay or improvement of Bruch's membrane function-related diseases including a complex extract of red ginseng and sea cucumber or fractions thereof as an active ingredient.

In addition, the present invention is a complex extract of the ginseng and sea cucumber or fractions thereof; Or it provides a health functional food composition for improving eye health comprising a red ginseng and sea cucumber complex extract or fractions thereof as an active ingredient.

In the health functional food composition of the present invention, the complex extract of ginseng / red ginseng and sea cucumber or fractions thereof, and the efficacy thereof are 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, the composition may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.

The kind of the food is not particularly limited, and includes all foods in a general sense. Non-limiting examples of foods that can be added to the material include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, dairy products, including other noodles, gums, ice cream, various soups, drinks, tea , A drink, an alcoholic beverage, and a vitamin complex.

When the health functional food composition of the present invention is a beverage composition, it may contain various flavors or natural carbohydrates and the like as an additional ingredient, as in a conventional beverage. Non-limiting examples of the natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweeteners such as dextrin, cyclodextrin; Synthetic sweeteners such as saccharin and aspartame; and the like. The proportion of the additional components added above may be appropriately determined by the choice of those skilled in the art.

In addition to the above, the nutraceutical composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin , Alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the health functional food composition of the present invention may contain a flesh for preparing natural fruit juice, fruit drink or vegetable drink. These components can be used independently or can be used in combination of 2 or more. The proportion of such additives may also be appropriately selected by those skilled in the art.

In addition, the present invention is a complex extract of red ginseng and sea cucumber or fractions thereof; Or it provides a method for preventing, delaying or treating a disease related to Brueck's membrane deterioration comprising administering to a subject a composition comprising a complex extract of ginseng and sea cucumber or a fraction thereof as an active ingredient.

The composite composition according to the present invention has the effect of slowing or reversing the aging process of the eye by improving the transport function of the Brueck membrane, removing lipid components deposited on the membrane, and promoting the regeneration of the Brueck membrane, thereby causing age-related macular lesions. It is excellent in preventing or treating various diseases caused by deterioration of the Bruch's membrane due to aging, including sex (AMD), and due to reduced transport of vitamins, metals and antioxidants, which are issued due to the maintenance of public health and aging. You can solve the problem.

1 is a diagram illustrating the cross-sectional image of the human retina and the components of phototransduction.

Figure 2 is a graph showing the structural changes of the Bruk's membrane due to aging, (A) the thickness of the Bruk's membrane increases by two to three times with age, (B) the accumulation of damaged or denatured collagen, and (C ) Major lipid substances, such as cholesterol esters, increase exponentially, and (D) free thiol groups decrease, causing aggregation of proteins.

3 is a diagram showing the change of Bruch's membrane due to aging and the rapid change in macular degeneration patients.

Figure 4 shows the mechanism of MMP action that plays a role in aging and regeneration of the Bruch's membrane and abnormal MMP action mechanism in macular degeneration patients.

5 is a result showing the change in hydraulic conductivity of the Bruch's membrane of the human due to aging of the general public and macular degeneration patients.

Figure 6 shows the change in the degree of diffusion of the Bruk's membrane in humans due to aging of the general population and macular degeneration patients.

Figure 7 is a result showing the effect of improving the transport function of Bruk's membrane of (A) red ginseng extract and (B) sea cucumber extract of the present invention.

Figure 8 is a result showing the effect of improving the repair conductivity of the Brueck membrane by repeated treatment of the red ginseng extract according to an embodiment of the present invention.

9 is a result showing the effect of improving the Bruch's membrane transport function of the red ginseng extract and sea cucumber extract of the present invention.

10 is a result showing the synergistic effect of the improvement of the Brux membrane transport function of the red ginseng and sea cucumber complex extract of the present invention.

11 is a dose response curve showing the lipid secretion effect from the Bruch membrane of the red ginseng extract and sea cucumber extract of the present invention.

12 is a (B) kinetic coefficient and (C) relative efficiency comparison table showing the lipid secretion effect on the various types of red ginseng extract and sea cucumber extract of the present invention in the Bruch's membrane.

Fig. 13 shows the result of removing free MMP enzyme from human Bruch's membrane.

14 is a result showing the removal effect of the MMP enzyme bound to the Bruk membrane of human using the red ginseng extract, sea cucumber extract and complex extract of the present invention.

15 is a result confirming that different types of MMP enzymes are secreted from the Bruch membrane waste when using the red ginseng extract and the sea cucumber extract of the present invention.

16 is a result of confirming the effect of delaying aging by adjusting the hydraulic conductivity curve by using the red ginseng and sea cucumber complex extract of the present invention.

17 is a result showing the synergistic effect of the improvement of the Bruch membrane transport function of ginseng and sea cucumber complex extract.

Referring to the present invention in more detail as follows.

Degenerative changes in the Bruch's membrane transport function due to aging cause vision problems in the elderly and, in severe cases, cause age-related macular degeneration (AMD) leading to blindness.

Numerous studies have shown that aging has a serious adverse effect on the material transport capacity and the waste removal process of the Brueck membrane (Hussain et al., 2002; 2004; 2010; Starita et al. 1996; Moore et al. 1995; Moore and Clover, 2001), it is known that waste accumulated in the Brueck's membrane due to aging is composed of lipids and denatured proteins. In addition, the root cause of waste accumulation in the Bruch's membrane was found to be due to the inability of proteolytic enzymes called matrix metalloproteinases (MMPs) to perform the role of the Bruch's membrane. .

MMP is a proteolytic enzyme that is secreted in the form of an inactive precursor (pro-form) from the RPE to the Bruch's membrane. The small peptides are removed from these precursors, resulting in activated MMP2 and active MMP9. Activated MMP2 and MMP9 enzymes can degrade most of the substances that make up the extracellular matrix through the activation process, removing the damaged components and replacing them with new ones. The mechanism of regeneration of the membrane plays a role in maintaining the structure and function of the Brooke membrane in a healthy state. However, it has been found that the amount of activated forms of MMP2 and MMP9 decreases due to the aging of the Bruch's membrane (Guo et al., 1999) .The amount of activated MMP2 and MMP9 in the Bruch's membrane of macular degeneration patients is similar to the mean age group. Compared to about 60% (Hussain et al., 2011).

Specifically, the mechanism of action of MMP according to aging is shown in FIG. 4. The precursor forms, pro-MMP2 and pro-MMP9, form a high molecular weight complexes (HMW) called HMW1 and HMW2 in the Bruch membrane through a polymerization reaction. These materials also combine with other pro-MMP2 and pro-MMP9 molecules to form larger polymers, called large macromolecular complexes (LMMCs) (Kumar et al., Hussain et al. 2010). As the synthesis of the polymer material increases due to aging, the polymer compound is trapped or bound in the matrix, and pro-MMP and active MMP are also trapped in the membrane and cannot be used. Therefore, since the amount of free MMP required for the Brueck membrane regeneration is reduced, the membrane is not degraded and regenerated normally. As a result, a considerable amount of waste accumulates, leading to a decrease in the transport capacity of the membrane.

The macular and peripheral areas of central vision were examined in the eyes of 56 healthy subjects in the range of 1 to 96 years and the eyes of 11 patients with macular degeneration. ) And their effects were evaluated.

First, the hydraulic conductivity of the Brueck membrane separated from the donated eye was measured to confirm the transport capacity of the waste. The separated Bruch membrane was placed in an open Ussing chamber (Ussing chamber) to measure the quantitative change of the fluid under hydrostatic pressure to calculate the change in hydraulic conductivity (FIG. 5B, C). As a result, the fluid transport capacity of the macular section decreased exponentially as aging progressed, and the transport capacity decreased by half every 16 years (FIG. 5D). The data in FIG. 5D is shown by converting the exponential decay linearly using a semi-log plot on the Y axis. In order to maintain the function of the cell, the Bruch's membrane requires a minimum hydraulic conductivity function, which is indicated by a failure line. This functional threshold can be determined by dividing the amount of fluid transported by the RPE by the hydrostatic pressure of the Brueck membrane. The hydraulic conductivity of the Brueck membrane required to deliver the RPE fluid can be calculated from the equation below.

Hydraulic Conductivity (HC) = fluid flow / pressure

However, hydrostatic pressure across a human Brukmak cannot be measured due to technical difficulties. In the case of monkeys, the pressure difference between the vitreous and the perichoroidal space was estimated to be about 4 mmHg (534 Pa) (Emi et al., 1989), which actually appears to be much lower. The value of 4 mmHg hydraulic conductivity required for transport ^{(0.1248 ml / hour / mm 2} ) a fluid to Brewer keumak by the RPE can be calculated as ^{0.65 x 10 -10 m / sec /} Pa.

If the transport function falls below this, fluid accumulates below the RPE, causing RPE exfoliation, leading to the death of the cell at the top. This symptom occurs in about 12 to 20% of patients with macular degeneration. Normally in normal people this line does not fall below the failure threshold for life, but in the general elderly population there is a crossing of this failure threshold, which can cause serious problems such as abnormal night vision. appear. In macular degeneration, it is impossible to measure the macular area independently because the macular area is significantly damaged by the nature of the disease. The hydraulic conductivity of the periphery was also similar to that of the macula, decreasing exponentially with a half-life of about 22 years (Fig. 5E). It can be seen that the hydraulic conductivity measured in the periphery of 11 patients with macular degeneration is all below the mean regression line (see black circle and red line in FIG. 5E), which is a serious condition of material transport loss even in the periphery rather than the macular area. It is showing progress.

Next, protein diffusion experiments were performed to confirm the nutrient transport capacity of the Brueck membrane. Specifically, the diffusion of the FITC-dextran (MW 23kDa) through the Brueck membrane was tested using a general Ussing chamber (Figure 6B, C). Dextran was chosen to be of a size similar to most carrier proteins that play a role in transporting substances such as vitamin A, trace metals, and lipids. Due to the aging of the Bruch's membrane, it was confirmed that the diffusion rate of the protein-sized material passing through the macula was sharply reduced (FIG. 6D). Because of this, despite the presence of normal vitamins and antioxidants in the plasma, the absence of these substances is observed in the macula. In the peripheral part, the degree of diffusion decreases slowly compared to the macula part (FIG. 6E), but in the case of macular degeneration, it was confirmed to decrease very rapidly (see black circle and red line of FIG. 6E). Thus, if the function of the macular part of the macular degeneration patient can be measured as compared with the degree of reduction of the peripheral part, it can be confirmed that the degree is much more rapid and rapid than the peripheral part. This reduction in diffusion transport interferes with nutrient supply and removal of hazardous wastes, which in turn increases the risk of damage and death of RPE and visual cells and causes blindness.

An object of the present invention is to improve the transport capacity of the Brueck membrane in the general elderly population and macular degeneration patients. This is done by removing the waste present in the membrane and reactivating the decomposition system on the membrane.

Clinically reported, the brook membrane aging of the elderly population is due to insufficient transfer of vitamin A value from the blood to RPE and the cell, leading to a decrease in the dark adaptation threshold. It will help you get all the nutrients you need. In the case of AMD patients, the transfer of nutrients, antioxidants, metals and vitamins and the removal of toxic wastes should be smoothly carried out in order to improve the transport capacity of the Bruch's membrane to avoid disease-causing metabolic damage.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as limited by these examples.

Example  1. Preparation of Red Ginseng Extract

When fresh ginseng is washed, steamed at 94 ~ 98 ℃, steam pressure 3 kg / ㎠, pressure 1.5 kg / ㎠, firstly dried at 60-70 ℃ for 12-20 hours, and when the moisture reaches 15-18% Red ginseng was prepared by daylight drying.

In order to prepare the solvent extract of the red ginseng, water, spirits, and a mixture of water and alcohol may be selected and extracted. In the first extraction, water was extracted in 5 to 10 times the weight of raw ginseng for 12 hours at 80 ~ 85 ℃, and in the second extraction, water was added in about 5 to 10 times the weight of raw ginseng. The extraction was carried out for 3 hours, and the third extraction was carried out with water 5 to 10 times the weight of raw ginseng and extracted for 8 hours at 80 to 85 ° C. The fourth extraction was carried out with water 5 to 10 times the weight of raw ginseng. Extraction was performed at 85 ° C. for 8 hours. Thereafter, the foreign matter was removed by filtration, cooled to 10 to 15 ° C., purified by centrifugation, and concentrated in vacuo to prepare a red ginseng extract for use in the present invention.

Example  2. Preparation of Sea Cucumber Extract

Dried sea cucumber was used to prepare sea cucumber powder using a grinder, and 70% ethanol was added thereto, followed by extraction for about 3 to 6 hours. Removing ethanol in a vacuum to prepare a sea cucumber extract used in the embodiment of the present invention.

Example  3. Different concentrations of red ginseng and sea cucumber extract Brooke Mak  Repair conductivity improvement effect

In order to evaluate the effect of red ginseng and sea cucumber extract on the transport function of Bruk's membrane, the Bruk's membrane isolated from four eyes ranging from 69 to 84 years was measured and represented as dose response curve for hydraulic conductivity improvement.

Specifically, the Bruch membrane is placed in an open-type Ussing chamber and passed through the Tris-HCl buffer under hydrostatic pressure through a tube, and after a certain time, the solution passed through the fluid transport (fluid transport) Was measured. The experimental group was treated with red ginseng extract by concentration of 0 to 10% or sea cucumber extract by concentration of 0 to 10%, and the fluid transport was measured again after incubation for 24 hours.

The graph shows the fold change of the reaction by extract concentration against the basal hydraulic conductivity measured before the reaction. As a result, as shown in Figure 7, both red ginseng and sea cucumber extract showed hyperbolic dose-response curves (hyperbolic dose-response curves) it was found that the hydraulic conductivity for the membrane is improved as the dose is increased. As a result, the kinetic parameters of the red ginseng extract showed Km = 0.7%, Vmax 3.17 fold change, and sea cucumber extract showed Km = 1.56%, Vmax 4.11 fold improvement. Therefore, the red ginseng and sea cucumber extracts were found to be in a saturation state showing the maximum effect of hydraulic conductivity improvement at the concentration of about 3%, respectively.

In saturation state, the hydraulic conductivity of red ginseng extract was increased by about 3 times and sea cucumber extract by about 3.2 times compared with that of no addition of each extract. It has been confirmed that it can have a significant effect on the improvement of transportation function.

Example  4. Repeated Treatment of Red Ginseng Extract Brooke  Repair conductivity improvement effect

To evaluate the effect of red ginseng extract on the transport function of Bruk's membrane when treated more than once, hydraulic conductivity measurement experiment was performed using the Bruk's membrane isolated from the eyes of donors 73 and 79 years old.

Specifically, the same method as in Example 3 was used, but only Tris-HCl was used as a control, and the experimental group was treated with 2.5% red ginseng extract, respectively. After the first culture, the fluid transport was measured, and further treated with 2.5% red ginseng extract, followed by incubation for 24 hours, and then the second measurement was performed.

The primary incubation of the Bruch's membrane with 2.5% red ginseng extract resulted in 1.94 x 10 ^-10 m / s / Pa at 0.91 x 10 ^-10 m / s / Pa and 1.36x 10 ^{-10 in} 79 year old donors. Repair conductivity was improved to 3.38 x 10 ^-10 m / s / Pa at m / s / Pa. When the red ginseng extract was treated twice, 73-year-olds from 1.94 x 10 ^-10 m / s / Pa to 2.68 x 10 ^-10 m / s / Pa (p <0.05). Significantly increased effect from 3.38 x 10 ^-10 m / s / Pa to 5.07 x 10 ^-10 m / s / Pa (p <0.005).

The results are shown in FIG. 8, but in the control group, there was no change in the first and second exposures, but the repeated transport of the red ginseng extract increased the transport capacity of the Bruch's membrane.

Example  5. Using red ginseng and sea cucumber extract Brooke Mak  Repair conductivity improvement effect

The red ginseng extract prepared in Examples 1 and 2 and the sea cucumber extract and the mixture was tested by the method of Example 3 using the Bruk membrane of the eyes of 12-89 year old eye donors to confirm the effect of improving the Bruch's membrane repair conductivity .

Specifically, the Bruch's membrane isolated from the eyes of 38 eye donors (12-89 years old) was incubated with 10% red ginseng extract for 24 hours, and Tris-HCl was used as a control. The results are shown in FIG. 9A, and it was found that the hydraulic conductivity of the Bruch's membrane was increased by 2.2 times by treating the red ginseng extract (control 1.11 ± 0.22 (n = 15, ○), 10% red ginseng extract treatment group 2.05). ± 0.38 (n = 23, marked); unit: 10 ^-10 m / s / Pa, p <0.001).

Next, the Bruch's membrane isolated from the eyes of 28 eye donors (52-84 years) was incubated with 2.5% sea cucumber extract for 24 hours, and Tris-HCl was used as a control. The results are shown in Figure 9B, it can be seen that the sea cucumber extract 2.3 times increased the hydraulic conductivity of the Brueck membrane (p <0.001).

In addition, in order to confirm the synergistic effect of the combination of red ginseng extract and sea cucumber extract, the Bruch membrane isolated from the eyes of 17 donors (ages 52 to 84) was treated with Tris-HCl buffer (control) and 3% red ginseng extract for 24 hours. , 3% sea cucumber extract or incubated with a mixture of red ginseng and sea cucumber extract, the results are shown in FIG.

As a result, the red ginseng extract and the sea cucumber extract improved the hydraulic conductivity of the Bruch's membrane in a similar manner (red ginseng: 2.15 ± 0.33 times increased, sea cucumber: 2.13 ± 0.47 times increased, Mean ± SD). Increased 2.89 ± 0.58 fold. From this, it was confirmed that there was a statistically significant improvement effect when the complex extract was treated compared to a single extract (p <0.001, Mean ± SD).

The improvement of the hydraulic conductivity of the red ginseng and sea cucumber extracts is the same as the effect that makes the Bruch membrane about 20 to 25 years young. This improvement in repair conductivity prevents the eye from going below the fail threshold, thereby reducing the risk of pathological progression such as macular degeneration or preventing vision deterioration due to aging.

Example  6. Using red ginseng and sea cucumber extract Brooke Mak  Lipid Waste Removal Effect

The main components of the lipid waste of the Bruch's membrane are cholesterol esters, cholesterol, triglycerides and phospholipids. Dose-response experiments were conducted to determine whether red ginseng extracts and sea cucumber extracts were effective in removing lipid extracts accumulated on Bruch's membrane.

Specifically, homogenized by mixing the Bruch membrane separated from the eyes of four donors (50-82 years old) Tris-HCl buffer, and centrifuged to separate the insoluble pellets containing the supernatant and lipid waste. The separated pellets were re-mixed with Tris-HCl buffer and incubated with red ginseng extract or sea cucumber extract at 0-2.5% concentration in a 37 ° C incubator for 24 hours. After the incubation, the sample was centrifuged and the amount of lipid secreted from the pellet into the supernatant was quantified by thin layer chromatography (TLC) on a silica gel plate.

As a result, dose response curves of various types of lipid secretion, lipid secretion data, and kinetics are shown in FIGS. 11 and 12. As shown in FIG. 11, when incubated with the red ginseng extract and the sea cucumber extract, the cholesterol esters, cholesterol, triglycerides and phospholipids deposited on the Bruch's membrane were secreted to remove various types of lipids from the membrane. Both extracts were found to reach saturation with maximum effect at a concentration of about 2.5%. In addition, as a result of comparing the lipid secretion data (Fig. 12A) and the secretion effect (Fig. 12B) of each extract, two complexes to remove the lipid waste of the Bruk's membrane because the removal effect of the red ginseng extract and sea cucumber extract is different depending on the lipid type It was confirmed that the composition consisting of the most effective.

Example  7. Using red ginseng and sea cucumber extract Brooke MMP  Enzyme secretion effect

The MMP enzyme of the Bruch's membrane exists in free form or bound to the membrane. In order to confirm that red ginseng and sea cucumber extract can remove the MMP enzyme from the Bruch's membrane, MMP bound to the membrane was first identified in the separated Bruch's membrane.

 The separated Bruch membrane was placed in an open Ussing chamber to flow through the Tris-HCl buffer to remove free materials. The fluid passing through the membrane was measured every hour and the amount of secreted MMP was confirmed by gelatin zymography. After completion of the experiment, a Bruch membrane of 6 mm in diameter was cut out to measure the MMP content.

Free MMPs were removed within 1 hour after the start of perfusion, and then slowly secreted to remove almost all free MMPs within 5 hours of perfusion (FIG. 13). Once the free MMP was released from the membrane, the Bruch membrane was separated from the chamber and the remaining MMP was extracted using the SDS buffer. Soluble or freely present MMP material was secreted slowly between 5 and 12 hours of perfusion, but most MMPs in the Bruch's membrane are removed after 5 to 12 hours of perfusion because they remain bound or trapped in the membrane. It could be confirmed that it remained on the membrane without being.

To see if these MMPs, bound or confined to the membrane, could be removed by red ginseng and sea cucumber extracts, the Bruch membrane isolated from the eyes of donors 73 and 79 years old was subjected to perfusion with Tris-HCl for 12 hours. The free MMP was first secreted and removed. Thereafter, the mixture was perfused with red ginseng extract (RG) at 2.5% concentration, sea cucumber extract (SC) at 2.5% concentration, and mixed extract (RG + SC), and after 24 hours, perfused with Tris buffer and the amount of secreted MMP was gelatinized. Confirmed by emoography.

As a result, as shown in Figure 14, it was confirmed that the MMP bound to the membrane is secreted when the red ginseng extract (RG), sea cucumber extract (SC) and the combination of the red ginseng and sea cucumber extract (RG + SC). It can be seen that the MMP of the control group (C) was observed in FIG. 14, but the MMP in the free state was not completely removed even after 12 hours of perfusion. Nevertheless, it was found that the Bruch membrane using 2.5% red ginseng extract (RG) effectively secreted MMPs bound to membranes such as HMW1, inactive and active forms of MMP 2 and MMP 9. 2.5% sea cucumber extract (SC) had a similar MMP secretion effect as red ginseng extract, and was particularly effective in removing a large amount of HMW2 bound to the membrane. The combination of red ginseng and sea cucumber extract (RG + SC) showed a much better effect on the removal of MMP bound to the membrane than red ginseng or sea cucumber alone extract, confirming the synergistic effect of the complex.

As described above, the complex of red ginseng and sea cucumber extract is the most effective for the removal of MMP enzyme trapped in the membrane, the combination of the extract acts to secrete a large molecular weight compound bound or trapped on the membrane to transport the Brueck membrane It's a great way to improve your skills. Most importantly, the removal of activated MMP2 and MMP9 can help normalize the membrane secretion system, which has the effect of degrading abnormal proteins, which aids in the regeneration of the Brueck membrane. In vivo, the enhanced porosity of the Brueck membrane, together with the new MMPs released by RPE, is expected to play an even more efficient role in the recovery and degradation of the Brueck membrane.

Example  8. Human eye using red ginseng and sea cucumber extract Brooke On pellet  Present MMP  Secretion effect of enzyme

In order to confirm the secretion effect of the MMP enzyme from the Bruk's membrane of red ginseng and sea cucumber extract, the Bruk's membrane of human eyes separated from two eyes of a 75-year-old donor was used. In the pellet of the Brueck membrane used as a sample, MMP enzymes were trapped or bound in the membrane. A certain volume of pellets were incubated with Tris-HCl buffer as a control, and the experimental group was incubated with 2.5% red ginseng extract or 2.5% sea cucumber extract. After incubation at 37 ° C. for 24 hours, centrifugation was performed to determine the amount of MMP secreted into the supernatant and the MMPs that remained bound to the pellets.

As a result, as shown in FIG. 15, the activated MMP2 and MMP9 were secreted slightly in the control group, and in the case of HMW2, most of them remained bound to the pellets. The red ginseng extract treated some secreted enzyme, but HMW2 still remained in the membrane, similar to the control. On the other hand, when the sea cucumber extract was treated, most of the HMW2 was secreted, and the activated forms of HMW1, MMP2 and MMP9 were also secreted. From this, it was found that sea cucumber extracts can activate HMW1 in the activated state and pro-MMP2 and pro-MMP9 in the precursor state from the membrane to remove wastes in the Bruch's membrane, which may have a positive effect on improving transport function.

The data confirmed in the above examples of the present invention clearly show that the red ginseng extract and the sea cucumber extract have the effect of improving the Bruch's membrane function, but the mechanism of action is different in lipid secretion and secretion effects of various MMP types present in the Bruch's membrane. . Therefore, it can be seen that the complementary effect is obtained when the two extracts are used as a complex than when they are used separately, and the experimental results of the complex extracts are remarkably effective in improving the structure and function of the Brueck membrane. I could confirm it.

The regeneration effect of the Bruch's membrane confirmed under these laboratory conditions will be further amplified through additional action with RPE in vivo. Therefore, these extracts raise the functional curve decaying with aging through the improvement of the substance transport capacity of the Brueck membrane, thereby providing the possibility of treatment of various diseases and visual degradation due to aging. Since there are individual differences in the reactions to the substances and the composition of lipid wastes of each person is different, the combination of ginseng / red ginseng and sea cucumber extracts may be ideally used to overcome heterogeneity.

Specifically, the treatment strategy proposed in the present invention is to improve the material transport ability due to aging as shown in Figure 16 to increase the straight line upwards. A 1.5-fold improvement in hydraulic conductivity would make the Bruchmak's function nine years younger, and a four-fold improvement in hydraulic conductivity would improve the donor's eye function for 32 years. Accordingly, the degree of improvement can be determined according to the age group targeted for treatment. For the general population who do not yet have visual ailments, lower doses can help maintain eye health, while older people can use higher doses to prevent aging and the associated disorders of Brueck's function. In patients with signs of eye disease due to aging, much higher doses can be used to delay or treat the progression of the disease.

Example  9. Using ginseng and sea cucumber extract Brooke Mak  Repair conductivity improvement effect

In order to confirm the synergistic effect of the combination of ginseng extract and sea cucumber extract, the Bruch's membrane separated from pig's eyes was treated with Tris-HCl buffer (control), 0.5% ginseng extract, 0.5% sea cucumber extract or ginseng and sea cucumber extract for 24 hours. Incubated with the mixture, the results are shown in Table 1 and FIG. 17.

As a result, ginseng extract and sea cucumber extract improved the hydraulic conductivity of the Bruch's membrane in a similar manner (Ginseng: 1.81 ± 0.18 times increased, Sea cucumber: 2.32 ± 0.05 times increased, Mean ± SD). 3.58 ± 0.65 fold increase. From this, it was confirmed that there was a statistically significant improvement effect when the composite extract was treated compared to a single extract (p <0.05, Mean ± SD).

	Mean	SD	n
Control	1.36	0.26	11
0.5% White Ginseng	1.81	0.18	3
0.5% SC	2.32	0.05	4
0.5% White Ginseng + SC	3.58	0.65	3

Claims (13)

1. Complex extract of red ginseng and sea cucumber or fractions thereof; or

   A pharmaceutical composition for preventing, delaying or treating a disease related to decreased Bruch's membrane function comprising a complex extract of ginseng and sea cucumber or a fraction thereof as an active ingredient.
2. The method of claim 1,

   The active ingredient is a pharmaceutical composition for preventing, delaying or treating a disease related to Brueck's membrane deterioration, characterized in that to improve the transport function of the Bruk's membrane.
3. The method of claim 2,

   A pharmaceutical composition for preventing, delaying or treating a disease related to Brueck's membrane deterioration, characterized in that the transport function is improved by improving the hydraulic conductivity or the substance diffusion function of the Brucke's membrane.
4. The method of claim 2,

   A pharmaceutical composition for preventing, delaying or treating a disease related to Brueck's membrane deterioration, characterized by improving transport function by removing proteins or lipids bound or trapped in the Bruk's membrane.
5. The method of claim 1,

   The active ingredient is a pharmaceutical composition for preventing, delaying or treating a disease related to Brueck's membrane function, which is characterized by regenerating the Bruch's membrane and improving the Bruch's membrane function.
6. The method of claim 5,

   The active ingredient regenerates the brux membrane by removing high molecular weight complexes 1 (HMW1), high molecular weight complexes 2 (HMW2) or lipid components bound or deposited on the bruc membrane, and improves the bruc membrane function. A pharmaceutical composition for preventing, delaying or treating a disease related to Brueck's membrane function.
7. The method of claim 5,

   The active ingredient is pro-MMP2 (pro-matrix metalloproteinases 2), pro-MMP9 (pro-matrix metalloproteinases 9), active matrix metalloproteinases 2 (active MMP2) and active matrix metalloproteinases (MMP9) active matrix A pharmaceutical composition for preventing, delaying, or treating a disease related to Brueck's membrane deterioration, characterized by regenerating the Bruch's membrane by secreting the same, and improving the Bruch's membrane function.
8. The method of claim 5,

   The active ingredient prevents, delays, or prevents Bruch's membrane deterioration-related diseases, which is characterized by regeneration of the Bruch's membrane by activating active MMP secretion from retinal pigment epithelium (RPE) and improving the Bruk's membrane function. Therapeutic pharmaceutical composition.
9. The method of claim 1,

   The composition of the present invention further comprises at least one composition selected from the group consisting of amino acids, antioxidants, vitamins, minerals, metals, lutein, astaxanthin, zeaxanthin, and bilberry extract. , Delayed or therapeutic pharmaceutical compositions.
10. The method according to any one of claims 1 to 9,

    The Bruch's dysfunction-related diseases include age-related macular degeneration (AMD), Sorsby's fundus dystrophy, ML (Malattia Levintanese), Stargardt disease, Best yolk-shaped macular dystrophy (Best's vitelliform retinal dystrophy) ) And DHRD (Doyne's honeycomb retinal dystrophy) is selected from the group consisting of a pharmaceutical composition for preventing, delaying or treating a disease related to Bruch's membrane deterioration.
11. Complex extract of red ginseng and sea cucumber or fractions thereof; or

    Health functional food composition for the prevention, delay or improvement of Bruch's membrane function-related diseases including a complex extract of ginseng and sea cucumber or fractions thereof as an active ingredient.
12. Complex extract of red ginseng and sea cucumber or fractions thereof; or

    Functional health food composition for improving eye health comprising a ginseng and sea cucumber complex extract or fractions thereof as an active ingredient.
13. Complex extract of red ginseng and sea cucumber or fractions thereof; Or a method comprising administering to a subject a composition comprising a complex extract of ginseng and sea cucumber or a fraction thereof as an active ingredient.

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