KR20140045260A - Composition for ginseng extract mediated retinal regeneration in normal ageing and macular degeneration - Google Patents

Abstract

The present invention relates to a composition comprising a ginseng extract as an active ingredient for delaying, preventing, and treating age-related macular degeneration and, more specifically, to a composition comprising a ginseng extract, which normalizes the function of the Bruch′s membrane of an eye, as an active ingredient for delaying, preventing, and treating age-related macular degeneration. The composition of the present invention removes substances deposited on the Bruch′s membrane and improves the transport function of the Bruch′s membrane so that the Bruch′s membrane may be regenerated through cell reactions in retinal pigment epithelium (RPE). The treatment of the present invention can prevent and treat functional eye failure as a result of degeneration with age. [Reference numerals] (AA) Fluid transport; (BB) Ginseng treatment; (CC) Macular degeneration(AMD); (DD) Function stop(Failure); (EE) Age(years)

Description

Composition for Ginseng Extract Mediated Retinal Regeneration in Normal Ageing And Macular Degeneration}

The present invention relates to a composition for the prevention and treatment of macular degeneration disease comprising ginseng extract as an active ingredient, and more particularly for the prevention and treatment of macular degeneration disease comprising a ginseng extract that normalizes the function of the Bruch's membrane as an active ingredient. It relates to a composition.

The present invention relates to a composition for the prevention and treatment of eye function degradation comprising ginseng extract as an active ingredient, and more particularly for the prevention and treatment of eye function degradation including a ginseng extract for normalizing the function of Bruk's membrane as an active ingredient. It relates to a composition.

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 this ginseng, has anti-aging, anti-inflammatory, antioxidant activity in the central nervous system and the cardiovascular and immune system (Wu JY, et al., J. Immunol., 148: 1519-25, 1992; Lee FC., Facts about ginseng, the elixir of life.Hollyn International.New Jersey, 1992; Huang KC., The pharmacology of Chinese herbs.CRC Press.Florida, 1999), antidiabetic activity (Chang HM., Pharmacology and application of Chinese material medica. Vol 1. World Scientific. Singapore, 1986) and anti-tumor activity (Sato K, et al., Biol. Pharm. Bull. 17: 635-9, 1994; Mochizuki M, et. al., Biol. Pharm. Bull. 18: 1197-1202, 1995). 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.

Ginsenosides, on the other hand, are metabolized by human intestinal microorganisms after ingestion and their metabolites are known to have various physiological activities (Karikura M, et al., Chem. Pharm. Bull, 39: 2357-61, 1991; Kanaoda M, et al., J. Tradit.Med. 11: 241-5, 1994; Akao T, et al., Biol. Pharm. Bull. 21: 245-9, 1998). For example, Rb1, Rb2, and Rc, the protoparnaxadiol-based saponins, are produced by human intestinal bacteria in 20-O--D-glucopyranosyl-20 (S) -protopanaxadiol (IH-901 , Compound K) (Hasegawa H, et al., Planta Medica 63: 463-40, 1997; Tawab MA, et al., Drug Metab. Dispos. 31: 1065-71, 2003) All-system saponins Re and Rg1 are metabolized by enterobacteria to ginsenoside Rh1 or ginsenoside F1 (Hasegawa H, et al., Planta Medica 62: 453-7, 1996; Tawab MA, et al., Drug Metab Dispos. 31: 1065-71, 2003), thus converted compounds K, Rh1 and F1 exhibit various physiological activities. Specifically, compound K is known to induce anti-metastatic or anti-cancer effects by preventing tumor invasion or preventing chromosomal alteration and tumor formation (Wakabayashi C, et al., Oncol. Res. 9: 411-7,1998; Lee SJ, et al., Cancer Lett. 144: 39-43, 1999), Rh1 has a cytotoxic effect on the growth of various cancer cells (Odashima S, et al., Cancer Res. 45: 2781-4, 1985; Ota T, et al., Cancer Res. 47: 3863-7, 1987; Lee HY, et al., Differentiation mechanism of ginsenosides in cultured murine F9 teratocarcinoma stem cells.Proc. 6th Int.Ginseng symp. Seoul 127-31, 1993 ) And anti-allergic, anti-inflammatory activity (Park EK, et al., Int. Arch. Allergy Immunol. 133: 113-120, 2004). In addition, F1 significantly reduces UV-B-induced cell death and downregulates expression of Bcl-2 and Brn-3a from apoptosis by irradiation of ultraviolet B. It is known to protect against (Lee EH, et al., J. Invest. Dermatol. 121: 607-13, 2003).

Macular degeneration is the leading cause of blindness in adults in developed countries. Around 30 million people worldwide suffer from this disease, and about half a million patients lose sight each year. In the West, about 40% of registered blind people aged 65 or older suffer from the disease. In Korea, glaucoma and diabetic retinopathy cause three major blindness, and the prevalence rate is gradually increasing due to the increase of elderly population. The time of onset is also decreasing from the 60s to the 4,50 in the elderly, and the incidence rate has also increased rapidly in recent years.

Eye disease caused by various changes in the macular area, which is very important for vision. This disease occurs mainly in older people over 50 years of age. It is an eye disease that can progress gradually with age and eventually cause blindness. . As the elderly population is on the rise, the frequency of occurrence is expected to increase.

Macular degeneration is an eye disease that progresses with age, causing damage to the macula in the center of the retina. The macula is the film of the camera and is responsible for the central vision. In the early stages of the disease, vision is blurred and near vision becomes distorted. Later, blindness occurs.

The eye cell receives light stimuli and transmits the information to the brain to recognize objects. Since eye cells are the most metabolic cells in the body, effective nutrient delivery and waste removal are essential. In addition, due to the nature of the environment rich in essential fatty acids, light, high concentrations of oxygen, it is mostly damaged by free radicals. Seed cells use retinal pigment epithelium (RPE) to continuously regenerate the outer segments of damaged seed cells.

Eye cells and RPE cells are supplied with nutrients through the blood circulation of the choroid (Fig. 1). When nutrients from the blood are secreted from the capillaries of the choroid, they must first pass through the extracellular matrix, the 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. Vitamins, trace metals, and lipids bind to carrier proteins, which are then separated from the RPE through the Bruch's membrane. Waste products from the cells and RPE pass through the Bruch's membrane and are removed into the choroid.

Aging increases the thickness of the Bruch's membrane, and deposits of lipids, proteo-lipid complexes, and wastes discarded from the RPE. In addition, cross-linking of collagen occurs frequently, the amount of denatured collagen increases, glycosylation of proteins and lipids caused by glycosylation (AGE; advanced protein glycation end-products, ALE; advanced lipid glycation end-products. Free radical reactions significantly damage the Brueck membrane.

Sustained synthesis and degradation are essential for the regeneration of the Bruch's membrane, where the matrix metalloproteinase MMP is responsible for the degradation of the membrane (Figure 2). However, due to aging, the degradation through the MMP system is not sufficient. Abnormal collagen is accumulated. In addition, in patients with macular degeneration, the amount of activated active MMPs used for the breakdown of the Bruch's membrane is significantly reduced, resulting in structural and functional changes in the Bruch's membrane.

The membrane transport is reduced due to the aging of the Brueck membrane, so the transport of nutrients and the removal of waste products do not proceed smoothly. Fluid transport decreases exponentially with age, and its capacity is halved every 16 years (Figure 3a). Diffusion of protein molecules also decreases very rapidly with age (Figure 4a). In addition, the transport capacity of metabolites associated with transport proteins, such as vitamin A, trace metals and lipids, also decreases with age.

Decreased transport of the Brux membrane causes a decrease in metabolism. Inadequate supply of essential nutrients adversely affects the antioxidant mechanisms of RPE and cell cells, increasing the risk of eye damage. The reduced transport of the Brueck membrane has two consequences. First, although essential metabolites are normally present in the plasma, they are deficient in essential metabolic intermediates in the retina due to reduced transport. Second, free radical damage increases due to metal ions that are not transported because the metal carrier material is trapped in the Brueck membrane. And wastes such as lipo-proteinaceous debris discarded by RPE cannot be removed, blocking the Bruch's membrane.

Clinically, aging of the Bruch's membrane can lead to vitamin A regeneration, leading to lower scotopic thresholds. Currently, vitamin A is prescribed in some countries with the addition of metals and antioxidants. There are two problems with this method. The first is that only certain nutrients are added, so other essential nutrients remain scarce. Second, when a metal is added to the Brook film, which is not properly transported, the concentration of the metal in the Brook film is increased, resulting in even more damage. The ideal solution would be to facilitate the transport of the Brueck membrane, so that all the necessary nutrients present in the plasma were supplied.

In the case of macular degeneration, changes occur in the Brueck's membrane due to aging and the transport capacity is reduced at a much faster rate (FIGS. 3A and 4A). In addition, the fluid transport capacity of the Brueck membranes reaches the failure thresholds much faster. When the stop threshold is reached, the fluid no longer migrates to the Brueck's membrane, causing the RPE to peel off after it is deposited under the RPE. This increases the diffusion distance of metabolic intermediates between the eye cells and the Bruch's membrane, increasing the possibility of degeneration of the eye cells.

In patients with macular degeneration, the rate of diffusion of protein carriers decreases faster and the transport of substances decreases. This results in poor metabolism, and RPE produces more waste. Poor nutrient supply and poor removal of waste accumulate, leading to the death of cells and RPE cells.

Attempts have been made to treat deficiencies by administering large amounts of vitamin A, but they cannot be used continuously because of the toxicity of the vitamins. AREDS (Age-Related Eye Disease Study) formulations of vitamin and mineral additives, which have been in the US for more than 10 years, are still not proven effective. As mentioned earlier, the addition of metal materials only augments the problems the membranes have by depositing toxic metal materials on the Brueck membrane.

Prevention and treatment of macular degeneration is possible through improved Brueck's transport. The composition according to the present invention comprising ginseng / red ginseng extract and ginsenoside as an active ingredient shifts the downward curve of transport depicted in FIGS. 3A and 4A upwards (FIGS. 3B and 4B). . This improves the transport capacity of macular degeneration patients so that metabolism can proceed smoothly.

references

[1] Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkendal-Hansen B, DeCarlo A, Engler JA. (1993) Matrix metalloproteinases: a review. Crit. Rev. Oral Biol. Med. 4: 197-250.

[2] Handa JT, Verzijl N, Matsunaga H, Aotaki-Keen A, Lutty GA, te Koppele JM, Miyata T and Hjelmeland LM. Increase in the advanced glycation end-product pentosidine in Bruchmembrane with age. Invest. Ophthalmol. Vis. Sci. 1999; 40: 775-779.

[3] Holz FG, Sheraidah GS, Pauleikhoff D and Bird AC. Analysis of lipid deposits extracted from human macular and peripheral Bruchmembrane. Arch. Ophthalmol. 1994; 112: 402-406.

[4] Hussain AA, Lee Y, Zhang JJ, Marshall J. (2011) Disturbed matrix metalloproteinase activity of Bruchmembrane in age-related macular degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 52: 4459-66.

[5] Hussain AA, Starita C, Hodgetts A, Marshall J. (2010) Macromolecular characteristics of ageing human Bruchmembrane: implications for age-related macular degeneration (AMD). Exp. Eye Res. 90: 703-710.

[6] Hussain AA, Lee Y, Marshall J. (2010) High molecular weight gelatinase species of human Bruchmembrane: compositional analyses and age-related changes. Invest. Ophthalmol. Vis. Sci. 51: 2363-71.

[7] Hussain AA, Starita C, and Marshall J. (2004) Chapter IV. Transport characteristics of ageing human Bruchmembrane: Implications for Macular Degeneration. In: Focus on Macular Degeneration Research, (Editor O. R. Ioseliani). Pages 59-113. Nova Science Publishers, Inc. New York.

[8] Hussain AA, Rowe L, Marshall J. (2002) Age-related alterations in the diffusion of amino acids across the human Bruch complex. Journal of the Optical Society of America, A, Optics, Image Science, & Vision. 19 (1): 166-72.

[9] Karwatowski WSS, Jefferies TE, Duance VC, Albon J, Bailey AJ & Easty DL. Preparation of Bruchmembrane 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 AA, Marshall J. (2010) Increased sequestration of matrix metalloproteinases in ageing human Bruchmembrane: implications for ECM turnover. Invest. Ophthalmol. Vis. Sci. 51: 2664-70.

[12] Moore DJ and Clover GM. The effect of age on the macromolecular permeability of human Bruchmembrane. Invest. Ophthalmol. Vis. Sci. 2001; 42: 2970-2975.

[13] Moore DJ, Hussain AA, Marshall J. (1995). Age-related variation in the hydraulic conductivity of Bruchmembrane. Invest. Ophthalmol. Vis. Sci. 36 (7): 1290-7.

[14] Owsley C, Jackson GR, 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 G, Jackson GR, Heinburger DC, Piyathilake CJ, Klein R, White MF, 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 RS, van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PGH and de Jong PTVM. Morphometric analysis of Bruchmembrane, the choriocapillaris and the choroid in ageing. Invest. Ophthalmol. Vis. Sci. 1994; 35: 2857-2864.

[17] Starita C, Hussain AA, Pagliarini S, Marshall J. (1996) Hydrodynamics of ageing Bruchmembrane: implications for macular disease. Exp. Eye Res. 62 (5): 565-72.

[18] Steinmetz RL, Haimovici R, Jubb C, Fitzke FW, Bird A. Symptomatic abnormalities of dark adaptation in patients with age-related Bruchmembrane change. Br. J. Ophthalmol. 1993; 77: 549-554.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for delaying, preventing and treating macular degeneration disease comprising ginseng extract as an active ingredient.

Another object of the present invention to provide a health functional food composition for preventing macular degeneration disease comprising ginseng extract as an active ingredient.

It is an object of the present invention to provide a composition comprising ginseng extract as an active ingredient for improving eye function by reconstructing transport of the Bruch's membrane of the eye.

It is an object of the present invention to provide a composition comprising ginseng extract as an active ingredient for improving the deterioration of degenerative eye function in the general public.

In order to achieve the above object, the present invention provides a pharmaceutical composition for delaying, preventing and treating macular degeneration disease comprising ginseng extract as an active ingredient.

The present invention provides a health functional food composition for preventing macular degeneration disease comprising ginseng extract as an active ingredient.

The present invention provides a composition comprising ginseng extract as an active ingredient for reconstructing transport of the Bruch's membrane of the eye to improve eye function.

The present invention provides a composition comprising ginseng extract as an active ingredient for improving degenerative eye function degradation of the general public.

According to the present invention, the composition comprising the ginseng extract as an active ingredient removes the proteins bound to the Bruch membrane or trapped MMP enzymes present as a large compound, and removes lipids accumulated in the Bruch membrane. It also activates MMP secretion from retinal epithelial cells (RPE cells). As a result, the hydraulic conductivity and the diffusion effect (diffusion) are excellent, thereby improving the degenerative eye function of the general public and preventing and treating macular degeneration.

The composition according to the present invention removes substances deposited on the Bruch's membrane and improves transport to allow for the regeneration of the Bruch's membrane through cellular reaction in retinal pigment epithelium (RPE). It is also possible to prevent, prevent and treat functional failure of the eye due to the degenerative symptoms that appear with age. Decreased transport of vitamin A, essential metals and antioxidants through the Bruch's membrane causes geriatric vision disorders, which can be prevented by only taking the composition according to the present invention. The composition according to the present invention improves the transport of the Bruch's membrane in which aging progresses, and can prevent a decrease in vision of the elderly and macular degeneration patients. The composition according to the present invention is applicable to the general public to maintain vision health, and also has an effect of delaying or treating the progression of the disease in people at risk of developing macular degeneration and patients with macular degeneration. The composition according to the present invention removes the waste accumulated in the Brueck membrane, separates the enzymes necessary for the recovery of the membrane but is not used because it is bound to the membrane, and improves the regeneration ability of the Brucke membrane by activating RPE.

Figure 1 shows the structural and functional changes of the human Bruch's membrane due to aging as a structure of the retina.
Figure 2 shows the MMP mechanism of Bruch's membrane in humans due to aging (Hussain, AA, Lee, Y, Zhang, JJ, Marshall, J (2011) Disturbed Matrix Metalloproteinase Activity of Bruch's membrane in Age-Related Macular Degeneration. Ophthalmol Vis Sci 52 (7): 4459-4466)
Figure 3a shows the fluid transport changes of the Bruch's membrane with age in normal and macular degeneration patients.
Figure 3b shows that the fluid transport curve, which has been declining, is elevated by treatment of Rg1, Rb1, and compound K (compound K) as ginseng / red ginseng extract and ginsenoside, showing the effects of delaying onset of macular degeneration and preventing and treating effects.
Figure 3c shows the effect of improving the hydraulic conductivity (hydraulic conductivity) of the human Brueck membrane of red ginseng extract.
FIG. 3D shows the effect of red ginseng extract raising the fail threshold of the falling Brueck's transport curve.
Figure 3e shows the improvement of the hydraulic conductivity of the Bruch film on the types of red ginseng extract currently distributed (1, 2: Cheonjiyang, 3: Jeonggwanjang, 4: Geumsan Korean Red Ginseng Gold)
Figure 4a is a comparison of the changes in the diffusion function of the Bruk's membrane due to aging in the general population and macular degeneration patients.
Figure 4b shows that the falling diffusion curve (diffusion curve) is elevated by Rg1, Rb1 and compound K (compound K) as ginseng / red ginseng extract and ginsenoside, showing the delay in the development of macular degeneration and the prevention and treatment effect.
Figure 4c shows that the red ginseng extract improved the diffusion (diffusion) of the human Bruk's membrane.
Figure 4d shows that the falling diffusion curve rises from the failure threshold by the red ginseng extract.
Figure 5a shows the effect of red ginseng extract on the secretion of MMP enzymes bound or trapped in the Brueck membrane.
Figure 5b shows the effect of red ginseng extract on the secretion of proteins bound to the Bruch's membrane.
Figure 6 shows the effect of removing the lipid component of the Bruch's membrane on the red ginseng extract.
Figure 7 shows the secretion effect of MMP enzymes in porcine RPE by red ginseng extract and ginsenosides (compounds K, Rg1, Rb1).
Figure 8 shows the types of fractions by extraction process of ginseng extract.

The present invention uses ginseng extract to improve the transport of human Bruch's membrane. The ginseng extract improves the function of the Bruch's membrane by (a) improving the nutrient deficiency of the retina of the general elderly population (b) improving the degenerative eye function of the general population (c) preventing and reversing the progression of macular degeneration. Helps with healing Various components of Rg1, Rb1 and compound K (compound K) as ginseng / red ginseng extracts and ginsenosides have a wide range of effects on various diseases. The mechanism of action that improves the transport of Bruch's membrane associated with macular degeneration is described below.

Eye cells, RPE cells, the Bruch's membrane and choroid, and blood supply are the functional units of the eye. Nutrients such as vitamins, lipids, and metals are supplied from the blood to the RPE and the cell through the Bruch's membrane. Wastes, including fluids, are removed in the opposite direction. In other words, nutrients spread to choroid-RPE-cells and waste spreads in the opposite direction.

Aging increases the thickness of the Bruch's membrane, and deposits of lipids, proteo-lipid complexes, and wastes discarded from the RPE. The more serious problem is that proteins dimerize and polymerize and accumulate in the matrix of the Brueck's membrane. Matrix metalloprotease (MMP) is required for normal regeneration of the Bruch's membrane. Pro-MMP 2 and 9 are polymerized to form high molecular weight 1 (HMW1) and high molecular weight (HMW2) polymers. And these materials combine with other pro-MMP9 to form larger macromolecular matrix metalloproteinase compounds LMMC (large macromolecular complexes). Increases in these compounds and protein aggregates block the Brueck's membrane and eventually reduce the Brueck's transport.

Aging leads to thickening of membranes, such as lipoproteins. Substances that cannot be degraded in waste products delivered from RPE to RPE are deposited with lipofuscin (FIG. 1). The other fatty protein complex is called drusen (2 in FIG. 1) and accumulates on the surface of the Brueck membrane. This change due to aging decreases the transport of Brueck's membrane and adversely affects metabolism of the cell. Thus, eye dysfunction due to aging of the eye appears, and in patients with macular degeneration, the change is even more severe, resulting in the death of RPE and eye cells, eventually losing vision.

MMP is a proteolytic enzyme that is secreted into pro-forms that are inactivated from the RPE to the Bruch's membrane. The active forms, active MMP 2 and 9, allow for continuous membrane regeneration by matrix degradation. The amount of this activated form of MMP was significantly reduced in the Bruch's membrane in macular degeneration patients, leading to degenerative changes in the membrane. In the poisonous membrane, pro-MMPs are polymerized into high molecular weight complexes called HMW1 and HMW2. These are combined with pro-MMP to form a larger polymer, which is called large macromolecular complexes (LMMC) (Figure 2). All of these compounds are trapped or bound in the matrix, reducing the material transport pathway through the Brueck membrane. In addition to these compounds, Pro-MMP and active MMP are also trapped in the membrane and cannot be used. This polymerization and sequestration is not just limited to MMPs, but other proteins in the matrix are similar. This change adversely affects the function of the Brukmak.

In order to maintain eye function, the Bruch's membrane requires a minimum hydraulic transport function, indicated by a failure line (3 in FIG. 3A). If the rate of transport falls below this line, degenerative changes create serious problems for transportation. The aging of the Brueck's membrane shows an exponential drop in hydraulic conductivity, which can be confirmed in a straight line by converting to a log form (4 in FIG. 3A). Normally, in normal people, this line does not meet the failure threshold for life. However, even in the general elderly population, problems with abnormal night vision appear when crossed with this dysfunction threshold. Macular degeneration patients diverge from the drop line at about 40-50 years old (5 in FIG. 3A), with a much steeper slope leading to the malfunction threshold (6 in FIG. 3A). Disruption of metabolism causes the disease to progress rapidly to the degenerative stage of the disease.

There are two ways to avoid crossing the threshold lines. Lowering the threshold point or raising the falling hydraulic conductivity line. The threshold point cannot be lowered because it is the minimum material transport capacity required to maintain the cell. However, according to the composition of the present invention comprising the ginseng / red ginseng extract and ginsenoside Rg1, Rb1 and compound K (compound K) as an active ingredient can increase the downward curve. If, at about 50 years old, the treatment of a composition comprising Rg1, Rb1, and compound K (compound K) as ginseng / red ginseng extract and ginsenosides (7 in Fig. 3b), the normal drop curve is increased. Intersection with the malfunction threshold is encountered at an age far beyond the life of the average person (8 in Figure 3b). Similarly, the decline curve of macular degeneration patients (9 in FIG. 3b) shifts so that the age crossing the threshold is significantly slowed from “10 in FIG. 3b” to “11 in FIG. 3b”. As the ginseng / red ginseng extract and ginsenoside, Rg1, Rb1, and compound K (compound K) were used in anticipation of the extent to which the drop curve was increased according to the dose and the dose was expressed in dotted lines (FIG. 12B).

The diffusion function of the Bruch's membrane was measured by the transfer of dextran molecules (24KDa). The molecule is similar in size to albumin or a metal transport protein. Diffusion of the polymer decreases linearly with age and reaches a threshold of function failure between 80 and 100 years of age. Many older people who reach this threshold have problems with the substance transport function of the Bruk's Membrane and need supplementation with vitamins and minerals. In patients with macular degeneration, the extent of this decline appears much more rapidly (13 in Figure 4a) and the disease progresses to a serious condition.

As shown in Figure 3b, which shows a change in hydraulic conductivity, ginseng / red ginseng extracts and ginsenosides, Rg1, Rb1 and compound K (compound K) raise the decline curve of diffusion, resulting in a functional shutdown threshold within normal lifespan. Do not intersect at (Figure 4b). In patients with macular degeneration, the age meeting this threshold is extended by Rg1, Rb1 and compound K (compound K) as ginseng / red ginseng extract and ginsenosides, thereby preventing RPE and visual cells from retinal degeneration.

As ginseng / red ginseng extract and ginsenosides, Rg1, Rb1 and compound K (compound K) improved the hydraulic conductivity of the eye (Figures 3c, 3d, 2, 3). FIG. 3D is a graph showing the hydraulic conductivity of the Bruch's membrane treated with the basic hydraulic conductivity and the red ginseng extract on a semi-log scale. As with previously published studies, the basic hydraulic conductivity of eye aging declines exponentially as best-fit non-linear regression lines. Ginseng / red ginseng extract and Rg1, Rb1 and compound K (compound K) as ginsenosides raise this line to improve hydraulic conductivity (Table 2, Figure 3c, Figure 3d, Table 3). Looking at this line shift (14 in FIG. 3D), the red ginseng extract improves hydraulic conductivity by 25 years. That is, the treatment of red ginseng extract improves the conductivity of the sample and delays the point of intersection with the stop function threshold for 25 years.

Aging is known to decrease the diffusion of dextran through the Bruch's membrane linearly. The present inventors have seen a new diffusion of albumin due to aging, and the diffusion of albumin decreases exponentially (inset graph of FIG. 4D). The non-linear regression pattern between diffusion and age is plotted as a logarithmic graph, showing the control and red ginseng extracts, and the red ginseng extract increased the diffusion of the Bruch's membrane (Figure 4c). Raises the downward curve upwards by an average of 18 years (Figure 4d).

Increasing the amount secreted by removing proteins bound or bound in the Brueck's membrane allows for improved transport by regenerating the Brook's membrane function (FIG. 5b). In addition, in the case of removing the lipid substance of the Brueck membrane, it is possible to improve the transport by regenerating the function of the Brucke membrane (Fig. 6). As shown in Figures 5b and 6, the red ginseng extract removes proteins and lipids of the Bruch's membrane and helps the Bruch's membrane regeneration.

MMPs in the Bruchmak exist in free or bound form, the ratio of which is unknown. However, as the age increases, the combined forms of MMPs increase. Red ginseng extract increased the secretion of free MMP (4G in Figure 5a). In other words, red ginseng extract is effective in secreting a significant amount of bound HMW2, HMW1, proMMP9 and activated enzymes together. Among them, in the case of MMPs, the secretion of activated MMPs helps to regenerate the membrane by removing abnormal substances.

MMP is secreted into pro-enzyme, which is inactivated by RPE, and small peptides are isolated and activated through RPE. MMP9 is activated when cells have migrated or damaged and during neovascularization, and Active MMP2 is a constitutive enzyme that functions in the normal regeneration process of the Bruch's membrane. After culturing pig eye RPE cells, the culture medium was collected and the type and amount of MMP were measured by gelatin zymography (FIG. 7). Red ginseng extract increases the secretion of ProMMP9, decreases the amount of active MMP9, and increases the secretion of Pro MMP2 and active MMP2. Red ginseng extract also activates HMW1. Compound K increased the amounts of Pro MMP 2, Pro MMP 9 and active MMP 2, which can be used as a composition mixed with red ginseng extract to obtain very useful results. Furthermore, compound K and ginsenoside Rb1 are effective in increasing the secretion of active MMP2, a key enzyme necessary for the regeneration process that can improve the structural and functional parts of the Bruch's membrane. Or mixed with other ginsenosides would be effective. Rg1 increases the amount of pro-MMP9, which indicates that Rg1 affects the secretion of Pro-MMP9.

This secretion of MMP indicates that the substances trapped in the matrix of the Brueck's membrane have been removed to increase the aging of the retina, and the secretion of MMP regenerates and improves the function of the Brueck's membrane, thus increasing the repair conductivity of the eye. Delaying, preventing and treating aging of the retina.

The ginseng / red ginseng extract and ginsenoside Rg1, Rb1 and compound K (compound K) are polymerized in the Bruch membrane to degrade the Bruch's membrane and decompose substances that lose its function, trapped or bound in the Bruch's matrix. It helps to nourish the eyes and discharge waste products by secreting nutrients and wastes such as proteins and lipids, and to regenerate the function of the Brux membrane by regenerating MMPs to reenact enzymes such as regeneration of the Bruk membrane. Involved, it shows an effect of increasing the hydraulic conductivity of the eye, and eventually has the effect of delaying and treating the aging of the retina function by regenerating the function of the retina as well as preventing the aging of the retina.

Ginseng / red ginseng extract and ginsenosides Rg1, Rb1 and compound K (compound K) may be used alone or in combination of two or more of these components. In combination with ginseng or red ginseng extract, at least one selected from ginsenosides Rg1, Rb1 and compound K (compound K), the composition may be more advantageously mixed. In addition, the ginseng / red ginseng extract and ginsenoside according to the present invention as a active ingredient of Rg1, Rb1 and compound K (compound K) can be administered with other substances to help eye diseases.

In addition, ginseng extract, red ginseng extract, ginsenoside Rg1, ginsenoside Rb1, ginsenoside compound K is used for pretreatment of patients transplanting stem cells or RPE cells for the treatment of macular degeneration, and for the treatment of macular degeneration. Pre-treatment in patients undergoing nanopulse laser treatment may be helpful in treating macular degeneration.

The present invention is described herein as applied to ginseng or red ginseng for convenience of description. However, the present invention can be applied to all ginseng processed in various forms, such as ginseng, rice ginseng, white ginseng, taeguk ginseng, black ginseng, purified ginseng, enzymatically treated ginseng, fermented ginseng, red ginseng and fermented red ginseng, which are within the scope of the present invention. It is apparent to those skilled in the art that it is included in. As used herein, the term "ginseng" means Panax ginseng, P. quiquefolius, P. notoginseng, P. japonicus, P. trifolium, P. pseudoginseng ), Vietnamese ginseng (P. vietnamensis) and American ginseng (Panax quinquefolium), but is not limited thereto. Preferably, the ginseng used in the present invention is ginseng (Panax ginseng).

"Panax ginseng CA Meyer" used in the present invention is prepared by heating ginseng through steam or sun-dried, preferably steam, more preferably steamed ginseng at 98-100 ℃ for several hours, Ginseng is well dried around 60 ℃.

The conventional red ginseng manufacturing method and extraction method is that red ginseng is prepared by washing, screening, distilling, drying, Chichi-Il-gun, cooking, grading, root-wetting, pressing, re-drying, and packing. Extracting from 80 ℃ to 100 ℃ and concentrating at a high temperature of 60 ℃ to 90 ℃ is a common method (Jinan Red Ginseng Master Quality Management, 2011.1. Jinan Red Ginseng Research Institute (educational materials). Www.ijrg.re.kr )

As used herein, the term ginseng or red ginseng extract means all liquids derived from ginseng or red ginseng, such as ginseng or red ginseng extract and leaching liquid. Extracts used herein are conventional extraction solvents known in the art, preferably (a) water, (b) anhydrous or hydrous lower alcohols having 1 to 4 carbon atoms (e.g. methanol, ethanol, propanol, butanol, Normal-propanol, iso-propanol and normal-butanol, etc.), (c) a mixed solvent of the lower alcohol with water, (d) acetone, (e) ethyl acetate, (f) chloroform, (g) 1,3- It can be obtained using butylene glycol, (h) hexane, (i) diethyl ether, or (j) butyl acetate. Preferred solvents are methanol, ethanol, butanol and water, and the most preferred solvent is water.

The extract of the present invention includes not only those obtained by using the solvent described above, but also those obtained by additionally applying a purification process thereto. The extract of the present invention can be prepared in powder form by an additional process such as vacuum distillation and freeze-drying or spray-drying.

Ginseng extract improves the hydraulic conductivity of the Bruch's membrane. The ginseng water extract (fraction 7 of FIG. 8) and the final water layer extracted by ginseng solvent (fraction 6 of FIG. 8) are the most effective in improving the hydraulic conductivity of the Brueck membrane, and the methanol layer (fraction 1 of FIG. 8). ), Butanol layer (fraction 5 of Figure 8) was also effective in improving the hydraulic conductivity of the Brueck membrane.

As a ginseng / red ginseng extract and ginsenoside according to the present invention and a composition comprising Rg1, Rb1 and compound K (compound K) as an active ingredient is formulated in a conventional manufacturing method to prepare tablets, capsules, injections, etc. When the tablet is prepared by combining lactose, microcrystalline cellulose, magnesium stearate, and the like, and the active ingredient in a ratio of 1: 1, a tablet having activity for preventing and treating macular degeneration disease can be prepared.

In the preparation of such medicaments, it may be used as a crude drug extract itself, but may be prepared by mixing with a pharmaceutically acceptable carrier, a forming agent, a dilute, etc., and preparing it as a powder, granule, Is possible. In addition, Rg1, Rb1 and Compound K (compound K) as ginseng / red ginseng extract and ginsenoside according to the present invention have been used for food and medicinal use since ancient times. The patient's age, sex, health status, diet, time of administration, method of administration, rate of excretion, severity of the disease may be changed. In general, as ginseng / red ginseng extract and ginsenoside, Rg1, Rb1, and compound K (compound K) are preferably administered at about 0.1 to 100 mg per kg of body weight, and more preferably at 0.1 to 80 mg per kg of body weight. .

Therefore, the composition containing the active ingredient of the present invention is prepared in consideration of an effective amount range, and the unit dosage formulations thus formulated are prepared according to the judgment of the experts who need to monitor or observe the administration of the pharmaceutical agent, Specialized dosing regimens may be used or several doses may be administered at regular intervals.

According to another aspect of the present invention, the present invention provides a food for preventing macular degeneration disease, in particular a health functional food containing ginseng extract as an active ingredient.

In the present invention, "health functional food" refers to a food having a bioregulatory function such as prevention and treatment of diseases, biological defense, immunity, recovery from illness, and aging inhibition, and should be harmless to the human body when taken in the long term.

In order for the ginseng / red ginseng extract and ginsenoside of the present invention to be used for the prevention and treatment of macular degenerative diseases as described above, Rg1, Rb1 and compound K may be prepared by various methods known in the field of food science or pharmaceuticals And may be prepared in any food form that can be taken orally by mixing with itself or with a pharmaceutically acceptable carrier, excipient, diluent or the like. Preferably in the form of beverage, ring, granule, tablet or capsule.

The health functional food of the present invention may further include ingredients that are commonly added during food production and are food acceptable. For example, when the beverage is prepared, in addition to the plant extract of the present invention, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and the like may be further included.

The amount that can be included as an active ingredient of the health functional food according to the present invention may be appropriately selected according to the age, sex, weight, condition, symptoms of the disease of the person who wants to prevent and treat macular degeneration disease, preferably adult standard 1 It is good to include about 0.01g to 10.0g per day, and by ingesting a health functional food having such a content can be obtained to prevent macular degeneration.

Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for illustrating the present invention, and thus the scope of the present invention is not construed as being limited by these embodiments.

Preparation of Red Ginseng and Extract Preparation

The fresh ginseng is washed, steamed at 94 ~ 98 ℃, steam pressure 3kg / ㎠, pressure 1.5kg / ㎠, firstly dried at 60 ~ 70 ℃ for 12-20 hours, until sunlight reaches 15-18%. Dry to prepare red ginseng. Red ginseng is extracted from a solvent, and is typically selected by selecting one of water, alcohol, a mixture of water and alcohol. The first extraction puts water 5 ~ 10 times more than the weight of raw ginseng and extracts at 80 ~ 85 ℃ for 12 hours, and the second extraction adds water 5 ~ 10 times more than the weight of raw ginseng. Extraction time, 3rd extraction put water in about 5 ~ 10 times of the weight of raw ginseng and extract for 8 hours at 80 ~ 85 ℃, 4th extraction put water in about 5 ~ 10 times of the weight of raw ginseng, 80 ~ Extraction is carried out at 85 ° C. for 8 hours. After filtration to remove foreign matters, and cooled to 10 ~ 15 ℃, centrifuged to purify and concentrated in vacuo.

Ginsenoside Content of 10% Red Ginseng Extract Content (mg / 1mL) division Rg1 Re Rf Rg2 +
Rh1 Rb1 Rc Rb2 Rb3 Rd Rg3 Sum Primary
sample 0.09 0.13 0.10 0.16 0.57 0.22 0.21 0.04 0.09 0.18 1.80 Secondary
sample 0.05 0.08 0.07 0.11 0.46 0.17 0.19 0.05 0.11 0.11 1.40

Preparation of Ginseng Extract

Ginseng is purchased, washed with clean water and freeze-dried to make ginseng without moisture. Lyophilized ginseng was ground to powder and used for extraction.

 ① Water extraction

      The dried ginseng was boiled with water corresponding to 10 times the amount of the sample and extracted twice with 6 hours using a reflux condenser. The extract was filtered and the water extract dried through lyophilization.

       ②MeOH extract

      The dried ginseng was taken, and MeOH (L) was added thereto, followed by repeated extraction for 4 hours at 60 ° C., followed by filtration using filter paper. The filtrate was concentrated under reduced pressure at 40 ℃ to obtain a MeOH extract.

       ③fraction

The MeOH extract was suspended in water in the same order as in FIG. 8, followed by shaking with an equal amount of n -Hexane to obtain a hexane fraction. The aqueous layer obtained after the Hexane fraction was sequentially prepared using the same amount of CHCl ₃ , EtOAc and n-BuOH. Fractions. Each fraction was concentrated under reduced pressure to give n-Hexane, CHCl 3, EtOAc and n-BuOH fractions.

Effect of Ginseng Solvent Extract on the Hydroconductive Conductivity

Ginseng was extracted using a solvent as shown in FIG.

The Bruch membrane was placed in an open-type Ussing chamber and passed through the tube through a Tris-HCl buffer to collect the passed solution after a certain time to measure the fluid transport (Fluid transport). Tris-HCl in the control group, the experimental group was incubated with solvent-induced ginseng extract for 24 hours and then transported again ([1] Moore DJ, Hussain AA, Marshall J. (1995). Age-related variation in the hydraulic conductivity of Bruchmembrane.Invest.Ophthalmol.Vis.Sci. 36 (7): 1290-7. [2] Starita C, Hussain AA, Pagliarini S, Marshall J. (1996) Hydrodynamics of ageing Bruchmembrane: implications for macular disease.Exp.Eye Res. 62 (5): 565-72.)

After incubating the Bruch membrane isolated from human eyes with 0.5 ~ 2% ginseng extract for each solvent for 24 hours, the hydraulic conductivity of the membrane increased (Table 2). As a result of measuring the effect of the hydraulic conductivity of the Brueck membrane for each fractional substance, a hexane layer (fraction 2 of FIG. 8), a chloroform layer (fraction 3 of FIG. 8), an ethyl acetate layer (fraction 4 of FIG. 8) There was almost no effect at, and there was little effect at the methanol layer (fraction 1 of FIG. 8) and butanol layer (fraction 5 of FIG. 8). The layers that showed the best effect were ginseng hydrothermal extracted water layer (fraction 7, p <0.001 in FIG. 8) and ginseng solvent extract final water layer (fraction 6, p <0.01) in ginseng solvent. The hydraulic conductivity has been significantly improved.

Effects of Ginseng Extracts on the Hydraulic Conductivity of Bruch Membranes in Various Solvent Types Fraction number
(Figure 8) Concentration of fractions used
(Fraction concentration examined) Number of eye samples Ratio of hydraulic conductivity compared to base level
(Fold change in hydraulic conductivity over basal) valence
(Significance level) Control group - Incubate in Tris-HCl 18 1.1 ± 0.2 - Red Ginseng Extract
Whole Ginseng extract - 10% 4 1.68 ± 0.16 P < 0.001 Ginseng Butanol Layer
(butanol extract) 5 0.5-2% 7 1.20 ± 0.24 NS Ginseng Methanol Layer
(methanol extract) One 0.5-2% 8 1.19 ± 0.08 NS Ginseng water extract
(water extract) 7 0.5-2% 13 1.46 ± 0.36 P < 0.001 Ginseng Final Water Layer
(final extract) 6 1-2% 9 1.43 ± 0.42 P <0.01

Effect of Ginsenosides Rg1, Rb1 and Compound K on the Repair Conductivity of the Brueck Membrane

The experiment was carried out in the same manner as in Example 3, but the experimental group was incubated with ginsenosides for 24 hours, and then transported.

The Bruch membrane isolated from the human eye was incubated with Rg1, Rb1 and Compound K in ginsenosides for 24 hours after which the membrane's hydraulic conductivity was increased (Table 3). Compound K was used in the experiment at 190 ug / ml concentration and increased the hydraulic conductivity of the Brueck membrane (p <0.005, Table 3). Rg1 (200ug / ml) and Rb1 (200ug / ml) also improved the hydraulic conductivity of the Brueck membrane.

Effect of Ginsenosides Rg1, Rb1 and Compound K on the Repair Conductivity of the Brueck Membrane Concentration of fractions used
(Fraction concentration examined) Number of eye samples Ratio of hydraulic conductivity compared to base level
(Fold change in hydraulic conductivity over basal) valence
(Significance level) Control group  Incubate in Tris-HCl 18 1.1 ± 0.2 - Compound K 190 ug / ml 5 1.45 ± 0.15 P <0.005 Rg1 200 ug / ml One 1.2 - Rb1 200 ug / ml One 1.27 -

Effect of Red Ginseng Extract on the Improvement of Hydraulic Conductivity

In the same manner as in Example 3, but the experimental group was incubated for 24 hours with 10% red ginseng extract was measured for transportation.

After culturing the Bruch membrane isolated from human eyes (17 donors, 12-87 years) with 10% red ginseng extract for 24 hours, the hydraulic conductivity of the membrane increased by 2.2 times (Figure 3c). After hydraulic conductivity and red ginseng extract culture, the results showed the logarithmic plot of age and association of donors used (FIG. 3D). The transport here showed a decrease in exponential decline with best-fit non-linear regression lines. Incubation with red ginseng extract shifts this curve upwards (Figure 3b), thereby increasing the age at which this curve meets the failure threshold. The hydraulic conductivity after red ginseng extract treatment keeps young for 20-25 years. Thus, red ginseng extract improves the hydraulic conductivity of the Brueck membrane.

In addition, the hydraulic conductivity of the Bruch's membrane for the types of red ginseng extracts currently distributed (1, 2: Cheonjiyang, 3: Jeonggwanjang, 4: Geumsan Korea Red Ginseng Gold) was measured in the same manner as described above (Fig. 3e). As a result, all the red ginseng extracts in circulation improved the hydraulic conductivity of the Bruch's membrane. These results show that even if the extraction method of the red ginseng extract is improved, the improvement of the hydraulic conductivity of the Brueck membrane appears.

Improvement of Diffusion Function of Bruch Membrane Using Red Ginseng Extract

The Ussing chamber was used to raise the Bruch membrane in the middle of the chamber, 0.1 mm FITC-albumin (MW 65 kDa, Tris-HCl as a solvent) was charged on the Bruch membrane side, and Tris-HCl buffer was used on the other side. The diffusion function of the Bruch's membrane was measured at 490 nm with an absorbance of the amount of FITC-albumin (MW 65 kDa) shifted after 12 hours of incubation with a difference of 0.1 mM concentration. The control group was incubated with Tris-HCl and the control group for 10 hours with red ginseng extract for 24 hours and then measured for diffusion ([1] Hussain AA, Starita C, Hodgetts A, Marshall J. (2010) Macromolecular characteristics of ageing human Bruchmembrane: implications for age-related macular degeneration (AMD) .Exp. Eye Res. 90: 703-710. When cultured with red ginseng extract, the diffusion function of the Bruch's membrane was increased 1.9 times (p <0.001, 33 donors, 12-92 years old) (Fig. 4c). The basal level of diffusion showed an exponential decrease with increasing age. Age, basal diffusion (diffusion), the relationship between the diffusion (diffusion) after red ginseng extract culture can be confirmed by a log graph (Fig. 4d). When incubated with red ginseng extract, the diffusion-age relationship curve shifts upward and shows improvement in diffusion function. When cultured with red ginseng extract, the effect of rejuvenation (diffusion) is 16-21 years young. As such, red ginseng extract improves the diffusion (diffusion) function of the Bruch's membrane.

Removal Effect of MMP Enzyme Bound or Trapped on Bruch Membrane of Red Ginseng Extract

With the aging of the Bruch's membrane, more proteins are trapped in the membrane's matrix or bind to the membrane, reducing membrane transport. In particular, high molecular weight MMP species, which have a large molecular weight, are mostly present in combination with the membrane (Fig. 2). This reduces the amount of free MMPs necessary for the activation process, and the reduction of the activated MMPs adversely affects the regeneration of the Brueck membrane.

It was measured whether MMP bound form in the Bruch membrane can be secreted by the perfusion of the red ginseng extract (Fig. 5a). The human Bruch membrane-choroid was separated and perfused with Tris-HCl buffer for 30 hours to remove the free moving components present in the Bruch's membrane. In the control group (1T-4T, sampled every 10 hours), most of the free MMP was secreted at the first collection (1T) and decreased over time. Didn't exist. Subsequent perfusion with 10% red ginseng extract resulted in the release of most of the bound components described in the MMP pathway (4G in FIG. 5A). Active MMP 2 and 9, which play an important role in the regeneration of the Bruk's membrane, were also secreted. Red ginseng secretes substances bound to the matrix, which improves the transport of Brueck's membrane.

Removal Effect of Red Ginseng Extract Bound or Trapped Protein in Bruch Membrane

With the aging of the Bruch's membrane, more proteins are trapped in the membrane's matrix or bind to the membrane, reducing membrane transport. In the same manner as in Example 8, the human Bruch's membrane-choroid was separated and perfused with Tris-HCl buffer for 30 hours to remove free moving components present in the Bruch's membrane. Then, after perfusion with 10% red ginseng extract, the amount of secreted protein was quantified by the Bradford assay (FIG. 5B). The red ginseng extract was secreted by proteins bound to the Bruch's membrane, which helped improve its transport.

MMP Secretion Effect of Pig Eye RPE after Red Ginseng Extract Treatment

Remove the cornea, lens and vitreous from the pig's eyes, remove the retina, rinse the eye cup with PBS (phosphate buffered saline) buffer, and add each incubation buffer. Time incubation was performed. (37 ° C, 5% CO2) DMEM medium (DulbeccoMinimal Essential Medium), calf's placental calf serum, and antibiotics were used as the base medium. The solution was then run and run a zymography gel that can analyze the amount of gelatin degrading enzymes. In the control medium, the precursors (pro) MMP 2 and 9, and active MMP 2 and 9 can be seen to be continuously secreted from the RPE (Fig. 7). Incubation with 10% red ginseng extract for 6-24 hours increased the secretion of precursor MMP9 (pro-MMP9) but decreased the secretion of active MMP9. In contrast, the secretion of pro and active MMP2 increased. It also activated HMW1. The effect of the red ginseng extract is helpful for the regeneration of the Bruk's membrane.

Red ginseng extract was effective in increasing the secretion of active MMP2, an enzyme that is essential for the regeneration process to improve the structural and functional parts of the Bruch's membrane.

MMP Secretion Effect of RPE in Pig Eye after Ginsenoside (Compound K, Rg1, Rb1) Treatment

It carried out in the same manner as in Example 10. Compound K increased the amount of pro-MMP 2 and 9, and active MMP2, and this result will be very useful when using compound K in red ginseng (Fig. 7). The amount of activated HMW1 increased after Compound K treatment. Rg1 increased the amount of pro-MMP9, indicating that Rg1 affects the secretion of Pro-MMP9. Rb1 was effective in reducing the amount of pro-MMP9 but not in active MMP9. Rb1 increased the secretion of active HMW1. Rb1 increased pro-MMP2 and active MMP2.

Compounds K and Rb1 were effective in increasing the secretion of active MMP2, a key enzyme necessary for the regeneration process to improve the structural and functional parts of the Brueck membrane.

Lipid Removal Effect of Bruk Membrane Using Red Ginseng Extract

There is an active research on the increase of lipid deposition due to aging and the effect of the transport of Brueck's membrane. After perfusion with Tris-HCl buffer to remove the soluble substances in the human Bruch membrane-choroid, half of the samples were perfused with Tris-HCl and half with 10% red ginseng extract for 24 hours. Lipids extracted from chloroform: methanol (volume ratio 2: 1) by volume were separated from the tissue by thin layer chromatography on silica gel plates. Chloroform: methanol: acetic acid: water is half the plate at a volume ratio of 50: 30: 8: 3, and heptane: diethyl ether: acetic acid) was finished with a volume ratio of 70: 30: 2, and then stained with 0.2% amide black 10 B. Samples obtained by persisting with Tris-HCl contain cholesterol and two lipids. Samples perfused with 10% red ginseng extract did not show two lipids during cholesterol or Tris-HCl perfusion (FIG. 6). That is, after perfusion with red ginseng extract among the cholesterol esters, triglycerides, cholesterol and two other lipid substances that appeared in the control group (T in FIG. 6) (G in FIG. 6). Cholesterol and the two lipids did not appear. As such, the red ginseng extract removed lipids from the Bruch's membrane, which may help the regeneration process.

The following formulations are examples of the components and usages that can be used per day, and the invention is not limited thereto by way of example only.

1. Formulation 1a

0.01-10g Ginseng / Red Ginseng Extract

2. Formulation 1b

0-10g Ginseng / Red Ginseng Extract + 0-30mg Rg1 + 0-30mg Rb1 + 0-30mg Compound K

However, red ginseng extract or ginseng extract (1-2 g / day), and a small amount of Rg1, Rb1 and compound K are used for the purpose of maintaining the normal retinal function of the general population aged 30-50 years.

3. Formulation 2

0-10g Ginseng / Red Ginseng Extract + 0-50mg Rg1 + 0-50mg Rb1 + 0-50mg Compound K

However, people over 50 years old (ie, if the elderly) is used to mix the red ginseng extract or ginseng extract (1-3g / day) and Rg1, Rb1, compound K to maintain the normal retinal function.

4. Formulation 3

0-10g Ginseng / Red Ginseng Extract + 0-70mg Rg1 + 0-70mg Rb1 + 0-70mg Compound K

However, red ginseng extract or ginseng extract (2-4g / day) and Rg1, Rb1, in order to delay the onset and progression of the disease in people with high risk of developing macular degeneration disease (AMD) and patients in the early stage of retinal disease. Compound K is used in combination. It can be used as a pre-treatment for patients transplanting stem cells or RPE cells for the treatment of macular degeneration disease (AMD). By improving the transport capacity of the Bruch's membrane before transplantation, the viability of the cells after transplantation can be improved and the attachment of the cells can be improved. Perform 2-3 months before transplantation. It can be used as a pre-treatment in patients undergoing micro-nano pulse laser therapy for the treatment of macular degeneration disease (AMD). Because the laser procedure depends on the MMP response of the RPE, a combination 3 to help the RPE and the Brueck membrane is used 2-3 months ago.

5. Formulation 4

0-10g Ginseng / Red Ginseng Extract + 0-100mg Rg1 + 0-100mg Rb1 + 0-100mg Compound K + Vitamin A 800µg + Vitamin D 5µg + Vitamin E 12mg + Vitamin C 80mg + Zinc 10mg + Copper 1 mg

However, to use for the purpose of treating macular degeneration disease (AMD), red ginseng extract or ginseng extract (3-6g / day) and (a) Rg1, Rb1 and compound K are mixed and (b) daily recommended vitamins and minerals are added. Use it.

[Production Example 1]

Manufacture of tablets

Using ginseng or red ginseng extract or ginsenoside Rg1, Rb1 and compound K, oral administration tablets were prepared using the wet granulation method and the dry granulation method with the following composition.

Composition: Ginseng extract, red ginseng extract, or ginsenoside Rg1, Rb1 and compound K by selecting one or more 200mg, hard silicic anhydride 10mg, magnesium stearate 2mg, microcrystalline cellulose 50mg, sodium starch glycolate 25mg , Lactose 101 mg, povidone 12 mg, anhydrous ethanol appropriate amount.

[Production Example 2]

Injection preparation

Injections were prepared using the ginseng or red ginseng extract or ginsenoside Rg1, Rb1 and compound K with the following composition.

Composition: Ginseng extract, red ginseng extract, or ginsenoside Rg1, Rb1 and compound K by selecting one or more 100mg, mannitol 180mg, monohydrogen phosphate 25mg, purified water for injection 2974mg

[Production Example 3]

Manufacture of beverages

* Using a ginseng or red ginseng extract or ginsenoside Rg1, Rb1 and compound K to prepare a beverage as follows. Select one or more of ginseng extract, red ginseng extract, or ginsenoside Rg1, Rb1 and compound K 200 mg, vitamin C 75 mg, vitamin B2 4 mg, vitamin B6 3 mg, dietary fiber 1,000 mg, liquid fructose 20000 mg, emulsifier 100 mg and 50 mg of fragrance are mixed with purified water so that the volume is 50 ml. The final mixed solution clarified by passing the mixed solution through a filter of 2 ~ 3㎛ was pre-sterilized at 90-93 ℃ for 15-20 seconds, filled into a 50ml bottle, and sterilized after 15-20 minutes at 80-85 ℃. Completed.

LMMC (large macromolecular complex): A compound consisting of HMW1 (High molecular weight) and HMW2, MMP9, MMP2.
HMW1 and HMW2: homopolymers or heteropolymers of MMP2 and MMP9
MMP: matrix metalloprotease, a matrix metalloproteinase
pro-MMP: precursor matrix metalloprotease
active MMP: active matrix metalloprotease

Claims (54)

Pharmaceutical composition for the prevention, delay and treatment of macular degeneration disease comprising ginseng extract as an active ingredient. The pharmaceutical composition for preventing, delaying and treating macular degeneration disease according to claim 1, wherein the active ingredient activates MMP secretion from RPE cells. The pharmaceutical composition for preventing, delaying and treating macular degeneration disease according to claim 1, wherein the active ingredient regenerates, maintains, and improves the function of the Bruch's membrane. 4. The macular degeneration according to claim 3, wherein the active ingredient regenerates, maintains, and improves the function of the bruc membrane by increasing the hydraulic conductivity of the bruc membrane and improving the fluid transport function. Pharmaceutical compositions for preventing, delaying and treating diseases. The method of claim 3, wherein the active ingredient improves the diffusion function of the Bruch's membrane, thereby reproducing, maintaining, and improving the function of the Bruch's membrane by activating exchange of nutrients and wastes between RPE cells, eye cells, and choroids. Pharmaceutical composition for the prevention, delay and treatment of macular degeneration disease, characterized in that. The method of claim 3, wherein the active ingredient prevents, delays, and treats macular degeneration disease by regenerating, maintaining, and improving the function of the brux membrane by removing proteins bound or bound in the matrix of the brux membrane. Composition. The method of claim 3, wherein the active ingredient secretes proMMP2 and proMMP9 binding type and active MMP2 and active MMP9 active form in the matrix of the Bruch membrane, thereby increasing the amount of free MMP enzyme to free the damaged membrane A pharmaceutical composition for preventing, delaying and treating macular degeneration disease, characterized by regenerating, maintaining and improving the function of the Bruch's membrane while helping to regenerate. The pharmaceutical composition for preventing, delaying and treating macular degeneration disease according to claim 3, wherein the active ingredient regenerates, maintains, and improves the function of the Brueck membrane by removing lipid components deposited on the Brueck membrane. Composition. According to claim 3, The active ingredient prevents macular degeneration disease, characterized in that by activating the secretion of active MMP2 (active MMP2) secretion from RPE cells to reproduce, maintain and improve the function of the brux membrane , Delayed and therapeutic pharmaceutical compositions. The pharmaceutical composition for preventing, delaying and treating macular degeneration disease according to claim 1, wherein the ginseng extract is extracted by selecting one or more of water, ethanol, methanol and butanol as a solvent. The pharmaceutical composition for preventing, delaying and treating macular degeneration disease according to claim 10, wherein the ginseng extract is extracted by selecting water as a solvent. According to claim 1, The ginseng extract is Korea ginseng (Panax ginseng), hoegisam (P.quiquefolius), Jeonchisam (P. notoginseng), bamboo shoots (P. japonicus), trifolium (P.trifolium), Himalayan ginseng ( P. pseudoginseng), Vietnamese ginseng (P. vietnamensis) and American ginseng (Panax quinquefolium) is a pharmaceutical composition for the prevention, delay and treatment of macular degeneration disease, characterized in that the extract extracted by selecting one or more from the crowd. The pharmaceutical composition for preventing, delaying and treating macular degeneration disease according to claim 1, wherein the active ingredient further comprises vitamins and minerals. The method of claim 1, wherein the active ingredient ginsenoside Rg1, ginsenoside Rb1, ginsenoside compound K, further comprising at least one selected from the group consisting of prevention, delay and treatment of macular degeneration disease Pharmaceutical composition for. Health functional food composition for preventing macular degeneration disease comprising ginseng extract as an active ingredient. The health functional food composition for preventing macular degeneration disease according to claim 15, wherein the active ingredient activates MMP secretion from RPE cells. The health functional food composition for preventing macular degeneration disease according to claim 15, wherein the active ingredient regenerates, maintains, and improves the function of the Bruch's membrane. 18. The macular degeneration of claim 17, wherein the active ingredient regenerates, maintains, and improves the function of the brux membrane by increasing the hydraulic conductivity of the brux membrane and improving the fluid transport function. Health functional food composition for disease prevention. 18. The method of claim 17, wherein the active ingredient improves the diffusion function of the Bruch membrane Health functional food composition for preventing macular degeneration disease characterized by regenerating, maintaining and improving the function of the Bruch's membrane by activating the exchange of nutrients and waste between RPE cells, eye cells and choroid. 18. The method of claim 17, wherein the active ingredient secretes proMMP2 and proMMP9 binding type and active MMP2 and active MMP9 active in the matrix of the Bruch membrane, thereby increasing the amount of free MMP enzymes to damage the membrane Health functional food composition for preventing macular degeneration disease, characterized in that by regenerating, maintaining and improving the function of the Bruch membrane while helping to regenerate. 18. The health functional food composition for preventing macular degeneration disease according to claim 17, wherein the active ingredient regenerates, maintains, and improves the function of the brux membrane by removing proteins bound or bound in the matrix of the brux membrane. 18. The health functional food composition for preventing macular degeneration disease according to claim 17, wherein the active ingredient regenerates, maintains, and improves the function of the Brueck membrane by removing lipid components deposited on the Brueck membrane. 18. The prevention of macular degeneration disease according to claim 17, wherein the active ingredient activates the secretion of active MMP2 from RPE cells, thereby regenerating, maintaining, and improving the function of the brux membrane. Functional food composition for use. The health functional food composition for preventing macular degeneration disease according to claim 15, wherein the ginseng extract is extracted by selecting one or more solvents from water, ethanol, methanol and butanol. 25. The health functional food composition for preventing macular degeneration disease according to claim 24, wherein the ginseng extract is extracted by selecting water as a solvent. The health functional food composition for preventing macular degeneration disease according to claim 15, wherein the active ingredient comprises vitamins and minerals. The method of claim 15, wherein the ginseng extract is Korean ginseng (Panax ginseng), hoegisam (P.quiquefolius), Jeonchisam (P. notoginseng), bamboo shoots (P. japonicus), trifolium (P.trifolium), Himalayan ginseng ( P. pseudoginseng), Vietnamese ginseng (P. vietnamensis) and American ginseng (Panax quinquefolium) is selected from one or more extracts selected from the crowd consisting of health functional food composition for preventing macular degeneration disease. The health functional food composition for preventing macular degeneration disease according to claim 15, wherein the active ingredient further comprises one or more selected from the group consisting of ginsenoside Rg1, ginsenoside Rb1, and ginsenoside compound K. . A pharmaceutical composition for pretreatment of stem cell or RPE cell transplantation for the treatment of macular degeneration, comprising ginseng extract as an active ingredient. Pre-treatment pharmaceutical composition of micro-nano pulsed laser treatment for the treatment of macular degeneration, characterized in that the ginseng extract as an active ingredient. Pharmaceutical composition for the prevention and treatment of eye function deterioration to regenerate, maintain and improve the retinal function by regenerating, maintaining and improving the function of the Brux membrane, characterized in that the ginseng extract as an active ingredient. 32. The method of claim 31, wherein the active ingredient increases the hydraulic conductivity of the Brueck membrane and improves the fluid transport function, thereby regenerating, maintaining and improving the function of the Brueck membrane, thereby regenerating and maintaining the retinal function. And pharmaceutical compositions for the prevention and treatment of improving eye function. 32. The method according to claim 31, wherein the active ingredient removes proteins bound or bound in the matrix of the Brueck membrane, thereby regenerating, maintaining, and enhancing the function of the Brueck membrane, thereby regenerating, maintaining, and improving the retinal function. Prophylactic and therapeutic pharmaceutical compositions. 32. The method according to claim 31, wherein the active ingredient improves the diffusion function of the Bruch's membrane, thereby activating exchange of nutrients and wastes between RPE cells, eye cells, and choroids, thereby regenerating, maintaining, and improving the function of the Bruch's membrane. Pharmaceutical composition for the prevention and treatment of eye function degradation to regenerate, maintain and improve retinal function. 32. The method of claim 31, wherein the active ingredient secretes proMMP2 and proMMP9 bound and active MMP2 and active MMP9 active in the matrix of the Brueck membrane, thereby increasing the amount of free MMP enzyme to damage the membrane A pharmaceutical composition for the prevention and treatment of deterioration of the eye function by regenerating, maintaining and improving the function of the Bruch's membrane by helping to regenerate, thereby regenerating, maintaining and improving the retinal function. 32. The method of claim 31, wherein the active ingredient removes lipid components deposited on the Bruch's membrane, thereby regenerating, maintaining, and enhancing the function of the Bruch's membrane to restore, maintain, and enhance retinal function. Prophylactic and therapeutic pharmaceutical compositions. 32. The method according to claim 31, wherein the active ingredient activates the secretion of active MMP2 from RPE cells, thereby regenerating, maintaining, and enhancing the function of the Bruch's membrane, thereby regenerating, maintaining, and improving retinal function. Prophylactic and therapeutic pharmaceutical compositions. 32. The pharmaceutical composition of claim 31, wherein the active ingredient activates MMP secretion from RPE cells, thereby regenerating, maintaining, and enhancing the function of the Bruch's membrane, thereby regenerating, maintaining, and improving retinal function. 32. The method according to claim 31, wherein the ginseng extract is selected by extracting at least one of water, ethanol, methanol, and butanol as a solvent to regenerate, maintain and improve the function of the Brook membrane. Pharmaceutical compositions for the prevention and treatment of eye failure. 40. The method of claim 39, wherein the ginseng extract is selected by extracting water as a solvent to regenerate, maintain and improve the function of the Bruk's membrane to regenerate, maintain and improve the retinal function of the prevention and treatment of eye degradation Composition. The method of claim 31, wherein the ginseng extract is selected from Panax ginseng, P.quiquefolius, P. notoginseng, P. japonicus, P.trifolium, and Himalayan ginseng Regenerates, maintains, and improves the function of the Bruch's membrane, which is an extract extracted by selecting one or more from the group consisting of P. pseudoginseng, P. vietnamensis, and American ginseng (Panax quinquefolium). Pharmaceutical compositions for the prevention and treatment of eye function deterioration, maintenance and improvement. The function of claim 31, wherein the active ingredient further comprises one or more selected from the group consisting of ginsenoside Rg1, ginsenoside Rb1, and ginsenoside compound K. And improving and regenerating, maintaining and improving retinal function, the composition for preventing and treating ocular deterioration. Health functional food composition for the prevention of eye function degradation to regenerate, maintain and improve the retinal function by regenerating, maintaining and improving the function of the Brux membrane, characterized in that the ginseng extract as an active ingredient. 44. The method of claim 43, wherein the active ingredient increases the hydraulic conductivity of the Brueck membrane and improves the fluid transport function, thereby regenerating, maintaining, and improving the function of the Brook membrane, thereby regenerating and maintaining the retinal function. And health functional food composition for preventing the reduction of eye function to improve. 45. The method of claim 43, wherein the active ingredient removes proteins trapped or bound in the matrix of the Brueck's membrane, thereby regenerating, maintaining, and enhancing the function of the Brueck's membrane, thereby regenerating, maintaining, and improving retinal function. Preventive dietary supplement composition. 44. The method according to claim 43, wherein the active ingredient improves the diffusion function of the Bruch's membrane, thereby activating exchange of nutrients and wastes between RPE cells, eye cells, and choroids, thereby regenerating, maintaining, and improving the function of the Bruch's membrane. Health functional food composition for preventing the reduction of eye function by regenerating, maintaining and improving the retinal function. The active ingredient of claim 43, wherein the active ingredient secretes proMMP2 and proMMP9, which are bound, and active MMP2, and active MMP9, which are active in the matrix of the Bruch membrane, thereby increasing the amount of free MMP enzyme to free the damaged membrane. Health functional food composition for the prevention of deterioration of the eye function by regenerating, maintaining and improving the function of the Bruch's membrane by helping to regenerate. 45. The method of claim 43, wherein the active ingredient removes lipid components deposited on the Brueck's membrane, thereby regenerating, maintaining, and enhancing the Bruch's membrane to restore, maintain, and enhance retinal function. Preventive dietary supplement composition. 45. The method of claim 43, wherein the active ingredient activates the secretion of active MMP2 from RPE cells, thereby regenerating, maintaining, and enhancing the function of the Bruch's membrane to restore, maintain, and enhance retinal function. Preventive dietary supplement composition. The health functional food composition of claim 43, wherein the active ingredient activates MMP secretion from RPE cells, thereby regenerating, maintaining, and improving the function of the Bruch's membrane, thereby regenerating, maintaining, and improving retinal function. 45. The method according to claim 43, wherein the ginseng extract is selected by extracting at least one of water, ethanol, methanol, butanol as a solvent, and regenerates, maintains, and improves the retinal function. Health food composition for the prevention of eye failure. The health food composition of claim 51, wherein the ginseng extract is selected by extracting water as a solvent to regenerate, maintain, and improve the function of the Brook membrane. . 45. The method of claim 43, wherein the ginseng extract is Korean ginseng (Panax ginseng), hoegisam (P.quiquefolius), Jeonchisam (P. notoginseng), bamboo shoots (P. japonicus), trifolium (P.trifolium), Himalayan ginseng ( Regenerates, maintains, and improves the function of the Bruch's membrane, which is an extract extracted by selecting one or more from the group consisting of P. pseudoginseng, P. vietnamensis, and American ginseng (Panax quinquefolium). Health food composition for the prevention of eye function deterioration, maintenance and improvement. 45. The function of claim 43, wherein the active ingredient further comprises one or more selected from the group consisting of ginsenoside Rg1, ginsenoside Rb1, and ginsenoside compound K. And enhancing and regenerating, maintaining and improving retinal function, the health food composition for preventing eye degradation.

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