KR101539573B1 - Composition For Ginsenoside K Mediated Retinal Regeneration in Normal Ageing And Macular Degeneration - Google Patents

Abstract

The present invention relates to a composition for delaying, preventing and treating a macular degenerative disease which comprises a ginsenoside compound K (compound K) as an active ingredient. More particularly, the present invention relates to a composition for killing a ginsenoside compound K compound K) as an active ingredient for delaying, preventing and treating macular degeneration diseases.
The present invention relates to a composition for preventing and treating deterioration of eye function comprising a ginsenoside compound K (compound K) as an active ingredient, and more particularly to a composition for preventing and treating ocular dysfunction, ) As an active ingredient.
Degenerative changes in the transport function of the Bruch's membrane due to aging lead to visual disturbances in the elderly and cause severe macular degeneration (AMD), which eventually leads to blindness. The composition according to the present invention improves transport to remove substances deposited on the bruch membrane and enable regeneration of the bruch membrane through cellular reactions in the retinal pigment epithelium (RPE). This treatment is degenerative as it grows older, making it possible to prevent, prevent and treat functional failure of the eye. Decreased transport of vitamin A, essential metals and antioxidants through the bruch membrane is a cause of the aged visual acuity disorder, which can be prevented by the administration of the composition of the present invention. The composition according to the present invention improves the transport of the aged Bruch's membrane and can prevent the deterioration of visual acuity of the general elderly and macular degeneration patients. The composition according to the present invention is applicable to the general public to maintain visual health, and also has the effect of delaying or treating the degree of disease progression in patients with macular degeneration and those with macular degeneration. The composition according to the present invention removes wastes accumulated on the bruch membrane, separates the unused enzymes which are necessary for the recovery of the membrane but is bound to the membrane, and improves the regeneration ability of the bruch membrane through activation of the RPE.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing and treating macular degeneration diseases and for reducing ocular function through retinal regeneration by a ginsenoside compound K (Compound K)

The present invention relates to a composition for the prevention and treatment of macular degenerative diseases, which comprises a ginsenoside compound K (compound K) as an active ingredient, and more particularly to a composition for preventing and treating macular degenerative diseases comprising a compound K ) As an active ingredient. The present invention also relates to a composition for preventing and treating macular degenerative diseases.

The present invention relates to a composition for preventing and treating deterioration of eye function comprising a ginsenoside compound K (compound K) as an active ingredient, and more particularly to a composition for preventing and treating ocular dysfunction, ) As an active ingredient.

Ginseng is one of the medicines traditionally used in the treatment of various diseases in Asian countries such as China, Korea, and Japan. Ginseng saponin (ginsenoside), which is a major active ingredient of ginseng, has antioxidant activity, antioxidant activity, antioxidant activity in the central nervous system, cardiovascular system and immune system (Wu JY et al., J. Immunol., 148: 1999), antidiabetic activity (Chang et al., 1999), and diabetes mellitus (Chang et al., 1999) HM, Pharmacology and application of Chinese material medica. Vol. 1, World Scientific. Singapore, 1986) and antitumor 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, over 30 ginsenosides have been isolated from ginseng saponins, and protopanaxadiol has been found in the ginsenoside, which is a glycoside containing aglycone with a dammarane skeleton. Most of the ginsenosides Rb1, Rb2, Rc and Rd belonging to the saponin group and the ginsenosides Re and Rg1 belonging to the protopanaxatriol saponin belong to the majority.

On the other hand, it has been known that ginsenosides are metabolized by intestinal microorganisms after ingestion and their metabolites 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, protopanaxadiol-based saponins Rb1, Rb2, and Rc have been identified by human intestinal bacteria as 20-O-D-glucopyranosyl-20 (S) -protonanaxadiol , Compound K) (Hasegawa H, et al., Planta Medica 63: 463-40, 1997; Tawab MA, et al., Drug Metab. Dispos. 31: 1065-71, 2003) Re and Rg1, which are all-saponins, are metabolized by intestinal bacteria 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). The compounds K, Rh1 and F1 thus converted exhibit various physiological activities. Specifically, Compound K is known to induce antitumor or anticancer effects by preventing the invasion of the tumor or preventing chromosome transformation and tumor formation (Wakabayashi C, et al., Oncol. Res. 9: 411-7, 1998; Rh1 is 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 antiallergic and anti-inflammatory activities (Park EK, et al., Int. Arch., Allergy Immunol., 133: 113-120, 2004). In addition, F1 significantly reduces the death of ultraviolet-B-inducible cells and down-regulates the expression of Bcl-2 and Brn-3a from apoptosis by irradiation of ultraviolet B, (Lee EH, et al., J. Invest. Dermatol. 121: 607-13, 2003).

Macular degeneration is the leading cause of adult blindness in developed countries. About 30 million people worldwide suffer from this disease, and about 500,000 people die each year from the disease. In the West, about 40% of registered blind people aged 65 or older suffer from this disease. In Korea, glaucoma and diabetic retinopathy are the leading causes of blindness, and the prevalence is increasing due to the increase of the elderly population. The onset of the disease has also been on the decline from the 60s to the 450s, and the incidence has also increased in recent years.

It is an eye disease that occurs due to various changes in the macular area that is very important for visual observation. Especially it occurs in older people aged 50 years or older. It progressively progresses with age and eventually blindness can result in ocular disease . It is expected that the incidence of the elderly population will increase even more.

Macular degeneration is an eye disease that often progresses with age, and damage to the macular area at the center of the retina occurs. The macula is the part of the camera film that is responsible for the central vision. At the onset of the onset, the vision is blurred and the near vision is distorted.

The cytoskeleton accepts stimulation by light and transmits the information to the brain so that it can recognize the object. Because cytoskeleton is the most metabolically active cell in the body, effective nutrient delivery and elimination of waste products are essential. In addition, due to the nature of the environment in which essential fatty acids, light, and high concentrations of oxygen are abundant, they are substantially damaged by free radicals. The photoreceptors continuously reproduce the outer segments of damaged photoreceptors using retinal pigment epithelium (RPE).

The cytoskeletal and RPE cells are supplied with nutrients through choroidal blood circulation (Fig. 1). If the nutrients from the blood are secreted from the capillaries of the choroid, they must first pass through the Bruch membrane, an extracellular matrix, before reaching the RPE and the cytoskeleton. Small nutrients such as glucose, oxygen, and amino acids pass through the Bruch membrane by simple passive diffusion. Vitamins, trace metals, lipids bind to the carrier protein and then separate from the RPE through the Bruch's membrane. The wastes generated from the cytoskeleton and the RPE are removed through the bruch membrane and into the choroid.

The aging process increases the thickness of the Bruch's membrane, deposits of lipids, proteo-lipid complexes, and wastes discarded in the RPE. In addition, protein and lipid glycation end-products (AGEs) resulting from glycosylation and cross-linking of collagen frequently occur, and the amount of denatured collagen is increased. advanced lipid glycation end-products. The free radical reaction significantly damages the Bruch membrane.

Continuous synthesis and degradation is essential for the regeneration of the Bruch's membrane, which is responsible for the degradation of the membrane (Fig. 2). However, degradation through the MMP system is not sufficient due to aging, Abnormal collagen accumulates. It has also been reported that the amount of activated active MMP (active MMP) used in the breakdown of Bruch's membrane is significantly reduced in patients with macular degeneration, resulting in structural and functional changes in the Bruch's membrane.

Due to the aging of the bruch membrane, transport of the membrane is reduced, transport of nutrients and removal of waste products do not proceed smoothly. Fluid transport declines exponentially with age, and its capacity is halved every 16 years (Fig. 3a). The 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, lipids, etc., is also reduced with age.

A decrease in the transport of the bruch membrane causes a decrease in metabolism. Inadequate supply of essential nutrients adversely affects the antioxidant mechanism of RPE and cytoskeleton, increasing the risk of eye damage. The transport reduction of the Bruch membrane results in two consequences. First, despite the fact that essential metabolites are normally present in plasma, they exhibit a deficiency of essential metabolic intermediates in the retina due to reduced transport. Second, metal transport materials are trapped in the bruch membrane, causing free radical damage to increase due to untransferred metal ions. And it prevents the waste membrane such as lipo-proteinaceous debris, which is abandoned by RPE, from being removed.

Clinically, aging of the Bruch's membrane can cause problems with the regeneration of vitamin A, thus lowering the scotopic thresholds. Vitamin A is currently prescribed in some countries with the addition of metal and antioxidants, which has two problems. First, because only certain nutrients are added, other essential nutrients still remain in a deficient state. Second, when a metal is added to a bruch film which is not properly transported, the concentration of the metal in the bruch film is increased and the damage is further increased. The ideal solution is to facilitate the transport of the Bruch's membrane, allowing all the necessary nutrients in the plasma to be supplied.

In the case of macular degeneration, a change occurs in the bruch membrane due to aging and the transport ability declines much faster (Figs. 3a and 4a). The fluid transport capacity of the Bruch membrane also reaches failure thresholds much sooner. When the downtime threshold is reached, the fluid can no longer move to the bruch membrane, causing deposition of the RPE after deposition under the RPE. This is because the diffusion distance of the metabolic intermediates between the cytoskeleton and the bruch membrane is distant, which increases the possibility that the cytoskeleton is denatured.

In patients with macular degeneration, the rate of diffusion of protein carriers is reduced more rapidly and material transport is reduced. Because of this, metabolism does not proceed properly, and RPE produces more waste. Smooth nutrient supply and accumulation of wastes that can not be removed cause the death of oocyte and RPE cells.

There is an attempt to treat the deficiency by administering a large amount of vitamin A, but it is not continuously available because of the toxicity of the vitamin. The formulation of the Age-Related Eye Disease Study (AREDS), a vitamin and mineral supplement, that has been in the United States for over 10 years, has yet to prove its effectiveness. As described above, the addition of a metal material only increases the problems of the film by depositing a metal material which is toxic to the bruch film.

Prophylaxis and treatment of macular degeneration is possible through improvement of bronchial membrane transport. The composition of the present invention comprising ginseng / red ginseng extract and ginsenoside as an active ingredient shifts the downward slope of the transport depicted in FIGS. 3A and 4A upward (FIGS. 3B and 4B) . This improves the transport capacity of patients with macular degeneration, allowing metabolism to proceed smoothly.

references

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

[2] Handa JT, Verzijl N, Matsunaga H, Aotaki-Keena, 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 aging human Bruchmembrane: implications for age-related macular degeneration (AMD). Exp. Eye Res. 90: 703-710.

[6] Hussain AA, Lee Y, and 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. 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, and Marshall J. (2002) Age-related alterations in the diffusion of amino acids across the human Bruchcomplex. Journal of the Optical Society of America, A, Optics, Image Science, & Vision. 19 (1): 166-72.

[9] Karwatowski WSS, Jefferies TE, Duane 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.

Related macular degeneration and vision loss: a randomized, placebo-controlled, clinical trial of high dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration. AREDS report No. 8. Arch Ophthalmol. 2001; 119: 1417-36.

[11] Kumara, El-Osta, Hussain AA, Marshall J. (2010) Increased sequestration of matrix metalloproteinases in aging 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 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 aging. Invest. Ophthalmol. Vis. Sci. 1994; 35: 2857-2864.

[17] Starita C, Hussain AA, Pagliarini S, Marshall J. (1996) Hydrodynamics of aging 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 the patients with age-related Bruchmembrane change. Br. J. Ophthalmol. 1993; 77: 549-554.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for delaying, preventing and treating a macular degenerative disease which comprises a ginsenoside compound K (compound K) as an active ingredient.

It is still another object of the present invention to provide a health functional food composition for preventing macular degeneration diseases containing the ginsenoside K (compound K) as an active ingredient.

It is an object of the present invention to provide a composition comprising, as an active ingredient, a ginsenoside compound K (compound K) for improving the eye function by rebuilding the transport of the bruch membrane of the eye.

It is an object of the present invention to provide a composition comprising, as an active ingredient, a ginsenoside compound K (compound K) for improving the degenerative eye function deterioration of the general public.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for delaying, preventing and treating a macular degenerative disease comprising a ginsenoside K (compound K) as an active ingredient.

The present invention provides a health functional food composition for preventing a macular degeneration disease which comprises a ginsenoside compound K (compound K) as an active ingredient.

The present invention provides a composition comprising as an active ingredient a ginsenoside compound K (compound K) for reconstituting transport of the Bruch's membrane of the eye to improve eye function.

The present invention provides a composition comprising, as an active ingredient, a ginsenoside compound K (compound K) for improving the degenerative eye function deterioration of the general public.

According to the present invention, a composition comprising an active ingredient of a ginsenoside K (compound K) can be used for removing MMP enzymes present in a large compound with proteins bound or trapped in the membrane, do. It also activates MMP secretion from retinal epithelial cells (RPE cells). It has excellent hydraulic conductivity and diffusion effect, and it is excellent in general degenerative eye function deterioration and prevention and treatment of macular degeneration.

The composition according to the present invention improves transport to remove substances deposited on the bruch membrane and enable regeneration of the bruch membrane through cellular reactions in the retinal pigment epithelium (RPE). It also helps prevent, prevent and treat functional failure of the eye due to the degenerative nature that develops with age. Decreased transport of vitamin A, essential metals and antioxidants through the bruch membrane is a cause of the aged visual acuity disorder, which can be prevented by the administration of the composition of the present invention. The composition according to the present invention improves the transport of the aged Bruch's membrane and can prevent the deterioration of visual acuity of the general elderly and macular degeneration patients. The composition according to the present invention is applicable to the general public to maintain visual health, and also has the effect of delaying or treating the degree of disease progression in patients with macular degeneration and those with macular degeneration. The composition according to the present invention removes wastes accumulated on the bruch membrane, separates the unused enzymes which are necessary for the recovery of the membrane but is bound to the membrane, and improves the regeneration ability of the bruch membrane through activation of the RPE.

Fig. 1 shows structural and functional changes of the human Bruch's membrane due to aging as the structure of the retina.
Figure 2 shows the MMP mechanism of the human Bruch's membrane due to aging (Hussain, AA, Lee, Y, Zhang, JJ, Marshall, J (2011) Disturbed Matrix Metalloproteinase Activity in Bruch's membrane in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 52 (7): 4459-4466)
Figure 3a shows the fluid transport changes of the Bruch's membrane with age of normal and macular degenerative patients.
FIG. 3B shows the delayed onset of the macular degeneration and the preventive and therapeutic effects of the fluid transport curve, which was lowered by the treatment of Rg1, Rb1 and compound K as ginseng / red ginseng extract and ginsenoside.
FIG. 3c shows the effect of improving the hydraulic conductivity of the human bruch membrane of red ginseng extract.
FIG. 3D shows the effect of red ginseng extract on increasing the failure threshold of the falling transport curve of the bruch membrane.
FIG. 3E shows the effect of improving the hydraulic conductivity of the Bruch's membrane against the kinds of red ginseng extracts currently in circulation. (1,2: Cheonjiyang, 3: Jeongkwanjang, 4: Geumsan Korean red ginseng gold)
FIG. 4A shows a comparison of changes in the diffusion function of the Bruch's membrane due to aging of the general and macular degeneration patients.
FIG. 4B shows that the falling diffusion curve is elevated by Rg1, Rb1 and compound K as Ginseng / Red ginseng extract and ginsenoside, delayed onset of macular degeneration, and prevented and treated.
4c shows that diffusion of human Bruch's membrane is improved by red ginseng extract.
Figure 4d shows that the falling diffusion curve rises from the failure threshold by the red ginseng extract.
5A shows the effect of red ginseng extract on the secretion of MMP enzymes bound or trapped in the bruch membrane.
Figure 5b shows the effect of red ginseng extract on the secretion of protein bound to the bruch membrane.
Fig. 6 shows the effect of removing the lipid component of the Brunei ginseng extract against red ginseng extract.
FIG. 7 shows the secretion effect of MMP enzyme on swine RPE by red ginseng extract and ginsenosides (compounds K, Rg1, Rb1).
FIG. 8 shows the kinds of fractions of the ginseng extract according to the extraction process.

The present invention is to improve the transport of the human Bruch's membrane using the ginsenoside compound K (compound K). (A) improvement of retinal nutrient deficiency in the elderly population; (b) improvement of degenerative eye function in the general population; (c) improvement of macular degeneration in the general population; Delays or reverses can help prevent and cure. Various components of Rg1, Rb1 and compound K as ginseng / red ginseng extract and ginsenoside have wide effect on various diseases. The mechanism of action to improve the transport of the Bruch's membrane associated with macular degeneration in this disease is described below.

Skeletal cells, RPE cells, Bruch's membrane, 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 cytoplasm through the Bruch's membrane. Waste containing fluid is removed in the opposite direction. That is, nutrient supply diffuses into the choroid-RPE-cytoplasm and waste expands in the opposite direction.

The aging process increases the thickness of the Bruch's membrane, deposits of lipids, proteo-lipid complexes, and wastes discarded in the RPE. A more serious problem is that proteins are dimerized and polymerized into the matrix of the Bruch's membrane. For the normal regeneration of Bruch's membrane, matrix metalloproteinase MMP (matrix metalloprotease) is required. Pro-MMP 2 and 9 are polymerized to form high molecular weight 1 (HMW1), high molecular weight 2 (HMW2) And these substances bind to other pro-MMP9 to form larger macromolecular matrix metalloproteinase compound LMMC (large macromolecular complexes), which is a larger compound. The increase of these compounds and protein aggregates blocks the Bruch membrane and eventually reduces the transport of the Bruch membrane.

Due to aging, substances such as fatty proteins accumulate in the membrane of the brain, resulting in thickening of the membrane. Substances that can not be degraded in the waste transferred from the cytosol to the RPE are deposited as lipofuscin (1 in FIG. 1). The other fat protein complex is called drusen (2 in FIG. 1) and is accumulated on the surface of the bruch membrane. Such changes due to aging reduce the transport of the Bruch's membrane and adversely affect the metabolism of the cytoskeleton. Thus, eye dysfunction due to aging of the eye occurs, and in patients with macular degeneration, the change becomes much more severe, resulting in the death of RPE and photoreceptors, eventually resulting in loss of vision.

MMP is a proteolytic enzyme that is secreted from the RPE into the bruch membrane as inactive pro-forms. Activated forms, active MMP 2 and 9, enable the continuous membrane regeneration by matrix degradation. The amount of this activated form of MMP was significantly reduced in the bruch membrane of patients with macular degeneration, leading to a degenerative change in the membrane. In the toxic environment, the bruch membrane, pro-MMPs are polymerized with high molecular weight complexes called HMW1 and HMW2. These are combined with pro-MMP to form larger and larger macromolecular substances, which are called large macromolecular complexes (LMMC) (Fig. 2). All of these compounds are either trapped or bound in a matrix to reduce the mass transport pathway through the bruch membrane. In addition to these compounds, Pro-MMP and active MMP can not be trapped in the membrane. Such polymerisation and sequestration are not limited to MMPs alone, but other proteins in the matrix also exhibit similar phenomena. These changes adversely affect the function of the Bruch membrane.

In order to maintain the eye function, the Bruch membrane requires a minimum hydraulic transport function, which is indicated by a Failure line (Fig. 3a, 3). If the transport speed drops below this line, there will be serious problems with transport due to degeneracy changes. The aging of the Bruch membrane shows an exponential decline with respect to hydraulic conductivity, which can be converted to a logarithmic form and confirmed as a straight line (Fig. 3a, 4). Normally, for a lifetime, this line does not meet with a failure threshold. However, among the general population of the elderly, when intersected with this functional threshold, there are problems such as abnormal night vision. The macular degenerated patient is diverted from the declination line at the age of 40-50 years (5 in Fig. 3A) and is directed to the functional stop threshold point at a much more steep slope (Fig. 3a, 6). Due to the obstruction of metabolism, the disease progresses rapidly to the degenerative stage of the disease.

There are two ways to avoid crossing the threshold lines. To raise the hydraulic conductivity line that lowers or drops the threshold point. The threshold point can not be lowered because it is the minimum material transport capacity necessary to maintain the cytoskeleton. However, according to the composition of the present invention containing ginseng / red ginseng extract and ginsenosides Rg1, Rb1 and compound K as an active ingredient, the falling curve can be increased. If the treatment of the composition containing the ginseng / red ginseng extract and Rg1, Rb1 and compound K as an active ingredient is started at about 50 years of age (7 in FIG. 3B), the ordinary decline curve is increased And the intersection with the functional suspension point is encountered at an age much out of the normal human lifetime (8 of FIG. 3B). Similarly, the falling curve of the macular degeneration patient (9 in FIG. 3b) migrates and the age of crossing with the threshold value is significantly delayed from "10 in FIG. 3b" to "11 in FIG. 3b". The degree of increase of the decline curve according to the usage and dosage of Rg1, Rb1 and compound K as ginseng / red ginseng extract and ginsenoside was expressed by a dotted line (12 in Fig. 3B).

The diffusion function of the bruch membrane was measured by the migration of dextran molecules (24 kDa). The size of this molecule is similar to the transport protein of albumin or metal. The diffusion of the polymer decreases linearly with age and reaches the point of functional dysfunction between the ages of 80 and 100 years. Many elderly people who have reached this threshold have problems with the substance transport function of the Bruch's membrane and need supplementation with vitamins and minerals to supplement them. In patients with macular degeneration, this decline is much more pronounced (13 in FIG. 4a) and the disease progresses to a severe condition.

As shown in FIG. 3B showing changes in hydraulic conductivity, Rg1, Rb1 and compound K as ginseng / red ginseng extract and ginsenoside increased the drop curve of diffusion, (Fig. 4B). In patients with macular degeneration, the age at which this threshold is met is extended by Rg1, Rb1 and compound K as ginseng / red ginseng extract and ginsenoside, thus preventing RPE and photoreceptor from retinal degeneration.

Rg1, Rb1 and compound K as ginseng / red ginseng extract and ginsenosides improved the hydraulic conductivity of the eyes (Fig. 3c, Fig. 3d, Table 2, Table 3). FIG. 3D is a graph showing the hydraulic conductivity and the hydraulic conductivity of the bruch membrane treated with red ginseng extract on a semi-log scale. Like previous published studies, the hydraulic conductivity of the eye with aging declines exponentially as the best-fit non-linear regression lines. Rg1, Rb1 and compound K as ginseng / red ginseng extract and ginsenoside increase this line to improve hydraulic conductivity (Table 2, Fig. 3c, Fig. 3d, Table 3). Looking at the movement of this line (14 in Figure 3d), red ginseng extract improves hydraulic conductivity by 25 years. In other words, the treatment of red ginseng extract improves the conductivity of the sample and delays the point of intersection with the functional stop point by 25 years.

It is known that the diffusion of dextran through the bruch membrane due to aging is linearly reduced. The present inventors have newly observed the diffusion of albumin due to aging, and the spread of albumin decreases exponentially (an insertion graph of FIG. 4d). When the non-linear regression form between diffusion and age is expressed as a logarithmic function graph, and the control group and the red ginseng extract are represented, the spread of the bruch membrane is increased by the red ginseng extract (FIG. 4c) Raises the drop curve upward for an average of 18 years (Fig. 4d).

Increased secretion by trapped or unbound proteins in the bruch membrane allows regeneration of the bruch membrane and improved transport (Fig. 5b). Also, removal of the lipid material of the bruch membrane can similarly improve the transport by regenerating the function of the bruch membrane (Fig. 6). As shown in FIG. 5B and FIG. 6, the effect of the red ginseng extract on the protein and lipid removal of the Bruch membrane helps to regenerate the Bruch's membrane.

The MMPs in the membrane are present in free form or in a conjugated form, the ratio of which is unknown. However, as age increases, combined MMPs increase. Red ginseng extract increased the secretion of free MMP (4G in Fig. 5A). In other words, red ginseng extract is effective to secrete significant amount of bound HMW2, HMW1, proMMP9 and activated enzymes together. In the case of MMP, secretion of activated MMP helps to regenerate the membrane by removing abnormal substances.

MMPs are secreted into the inactive pro-enzyme by RPE, and the small peptides are activated by RPE. MMP9 is activated when cells are moved or damaged, and when neovascularization occurs, and Active MMP2 is a constitutive enzyme that functions in normal regeneration of Bruch's membrane. After the RPE cells of the pig eyes were cultured, the culture medium was collected and the type and amount of MMP were measured by gelatinization (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, which is effective in cleansing the Bruch membrane. In addition, red ginseng extract activates HMW1. Compound K increased the amount of Pro MMP 2, Pro MMP 9, and active MMP 2, and when used as a composition mixed with red ginseng extract, very useful results can be obtained. Furthermore, compound K and ginsenoside Rb1 are effective in increasing the secretion of active MMP2, a key enzyme in the regeneration process that can improve the structural and functional parts of the Bruch's membrane. These two components are ginseng or red ginseng extract Or with other ginsenosides. Rg1 increases the amount of pro-MMP9, which indicates that Rg1 affects the secretion of Pro-MMP9.

These secretions of MMPs are trapped in the matrix of the Bruch's membrane, indicating that substances that increase the aging of the retina are being removed, and the secretion of MMPs regenerates and enhances the function of the Bruch's membrane, thereby increasing the hydraulic conductivity of the eye, To retard, prevent and cure the aging of the retina.

Thus, Rg1, Rb1 and compound K as ginseng / red ginseng extract and ginsenoside are polymerized in the bruch membrane to decompose the substances that degrade the bruch membrane and lose its function, It regulates the function of Bruch's membrane by releasing nutrients and waste materials such as proteins and lipids, supplying nutrients to the eyes, releasing waste products, and releasing MMPs to regenerate the function of the Bruch's membrane And thus exhibits an effect of increasing the hydraulic conductivity of the eye. Thus, it not only prevents the aging of the retina but also regenerates the function of the retina, thereby delaying and treating the aging of the retina.

The ginseng / red ginseng extract, ginsenosides Rg1, Rb1 and compound K can be used alone or in combination of two or more of these components. Compositions comprising at least one of ginsenosides Rg1, Rb1 and compound K, together with ginseng or red ginseng extract, and mixing them appropriately can exhibit more preferable effects. In addition, the composition containing the ginseng / red ginseng extract and the ginsenosides Rg1, Rb1 and compound K as an active ingredient according to the present invention can be administered together with other substances useful for eye diseases.

In addition, ginseng extract, red ginseng extract, ginsenoside Rg1, ginsenoside Rb1, ginsenoside K can be used for pretreatment of stem cell or RPE cell transplantation patients for macular degeneration treatment, It is more helpful to treat macular degeneration when used for pretreatment of patients undergoing nano-pulsed laser procedures.

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 kinds of ginseng processed in various forms such as ginseng, misham, white ginseng, taegeuk ginseng, black ginseng, purified ginseng, enzyme treated ginseng, fermented ginseng, red ginseng and fermented red ginseng, It is obvious to those skilled in the art. In the specification, the term "ginseng" includes Panax ginseng, P. quiquefolius, P. notoginseng, P. japonicus, P. trifolium, P. pseudoginseng , ≪ / RTI > P. vietnamensis and Panax quinquefolium. 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-drying, preferably steam, more preferably steam ginseng at 98-100 ° C for several hours, Means ginseng dried at around 60 ℃.

The conventional methods for preparing and extracting red ginseng are as follows: red ginseng is produced by processes such as washing-selecting ginseng-drying ginseng-cheimi-ilgan-cooking-grading-ginseng- It is a common method to extract at 80 to 100 DEG C and then to concentrate at a high temperature of 60 to 90 DEG C. (JINAN Ginseng Brand Quality Control, 2011. JINAN Ginseng Research Institute (Educational Materials) www.ijrg.re.kr )

In the present specification, the term "ginseng or red ginseng extract" means all liquids derived from ginseng or red ginseng, such as an extract and an extract of ginseng or red ginseng. The extracts used herein can be prepared by conventional extraction solvents known in the art, preferably (a) water, (b) anhydrous or hydric lower alcohol having 1-4 carbon atoms such as methanol, ethanol, propanol, (D) acetone, (e) ethyl acetate, (f) chloroform, (g) 1,3-propanediol, Butylene glycol, (h) hexane, (i) diethyl ether, or (j) butyl acetate. Among these, preferred solvents are methanol, ethanol, butanol and water, and the most preferable solvent is water.

The extract of the present invention includes not only those obtained by using the above-mentioned solvents, 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 membrane. The most effective way to improve the hydraulic conductivity of the bruch membrane with the ginseng water extract (Fraction 7 in FIG. 8) and the extraction final layer of ginseng solvent (Fraction 6 in FIG. 8) ), Butanol layer (Fraction 5 of FIG. 8) was also effective in improving the hydraulic conductivity of the Brunei membrane.

The composition comprising the ginseng / red ginseng extract and the ginsenoside Rg1, Rb1 and the compound K as an active ingredient according to the present invention is formulated into a tablet, a capsule, an injection or the like by the usual production method. When tablets containing lactose, microcrystalline cellulose, magnesium stearate and the like, which are used as a base in the production of a tablet, are used in a ratio of 1: 1, tablets having activity for preventing and treating macular degeneration can be produced.

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. Rg1, Rb1 and compound K as ginseng / ginseng extract and ginsenoside according to the present invention have been used for edible and medicinal purposes for some time, and there is no particular limitation on the dosage thereof, , Age, sex, health condition, diet, administration time, administration method, excretion rate, severity of disease, and the like. In general, the ginseng / red ginseng extract and ginsenoside Rg1, Rb1 and compound K are preferably administered in an amount of about 0.1 to 100 mg per 1 kg of body weight, and more preferably 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, there is provided a food for preventing macular degeneration diseases, particularly a health functional food, containing a ginsenoside compound K (compound K) as an active ingredient.

In the present invention, the term "health functional food" refers to a food having a biological control function such as prevention and treatment of diseases, bio-defense, immunity, recovery after disease and aging inhibition.

In order for the ginsenoside compound K of the present invention to be used for the prevention and treatment of macular degenerative diseases as described above, it may be prepared by various methods known in the field of food science or pharmaceuticals, May be prepared in any food form that can be ingested orally by admixture with acceptable carriers, excipients, diluents, and the like. Preferably in the form of beverage, ring, granule, tablet or capsule.

The health functional food of the present invention may further comprise ingredients that are conventionally added at the time of food production and which are pharmaceutically acceptable. For example, in the case of beverage preparation, one or more components may be further included in citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, etc. in addition to the plant extract of the present invention.

The amount that can be included as an active ingredient of the health functional food according to the present invention can be appropriately selected according to the age, sex, weight, condition, and symptom of a person who desires prevention and treatment of macular degenerative diseases, Day to about 10.0 g, and a health functional food having such a content may be ingested to obtain a macular degeneration preventing effect.

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.

Manufacture of red ginseng and production of extract

The fresh ginseng was washed and dried at 94 to 98 ° C, steam pressure of 3 kg / cm 2, pressure of 1.5 kg / cm 2, primary drying at 60 to 70 ° C for 12 to 20 hours, Dried to produce red ginseng. In extracting red ginseng from a solvent, usually one of water, alcohol, water and a mixture of water is selected and extracted. The first extraction is carried out at 80 ~ 85 ℃ for 12 hours with 5 ~ 10 times the amount of water. The second extraction is 5 ~ 10 times the weight of the raw material. And the third extraction is 5 ~ 10 times of the weight of the raw material, 8 ~ hour of extraction at 80 ~ 85 ℃, the fourth extraction is 5 ~ 10 times of the weight of the raw material, Extract at 85 ° C for 8 hours. After that, it is filtered to remove impurities, cooled to 10 ~ 15 ℃, centrifuged and concentrated in vacuo.

Ginsenoside content of 10% red ginseng extract Content (mg / 1 mL) 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

Manufacture of ginseng extract

Purchase ginseng, wash it with clean water, and freeze dry to make ginseng without water. The lyophilized ginseng was pulverized using a pulverizer and used for extraction.

 ① Water extraction

      The dried ginseng was boiled in water equivalent to 10 times the volume of the sample and repeatedly extracted twice for 6 hours using a reflux condenser. The extract was filtered, and then dried by freeze drying to obtain a water extract.

       ②MeOH extract

      The dried ginseng was taken and MeOH (L) was added thereto. The extract was repeatedly extracted twice at 60 ° C for 4 hours and filtered using a filter paper. The filtrate was concentrated under reduced pressure at 40 DEG C to obtain MeOH extract.

       ③ Fraction

8, the same amount of n- Hexane was added to the mixture, and hexane fraction was obtained by shaking. The hexane fraction was fractionated, and the aqueous layer obtained was fractionated with CHCl ₃ , EtOAc and n-BuOH in the same amount Fractionation. Each fraction was concentrated under reduced pressure to obtain n-hexane, CHCl3, EtOAc and n-BuOH fractions.

Improvement of Hydraulic Conductivity of Bruch Membrane by Ginseng Solvent Extract

Ginseng was extracted with a solvent as shown in Fig.

The bruch membrane is placed in an open-type Ussing chamber, passed through a Tris-HCl buffer through a tube, and the solution passed after a certain period of time is taken to measure the fluid transport. (1) Moore DJ, Hussain AA, and Marshall J. (1995). Age-related variation in the hydraulic conductivity of Tris-HCl in the control group and transport of the ginseng extract in the experimental group Bruchmembrane, Invest. Ophthalmol, Vis. Sci. 36 (7): 1290-7. [2] Starita C, Hussain AA, Pagliarini S, Marshall J. (1996) Hydrodynamics of aging Bruchmembrane: Res. 62 (5): 565-72.)

After incubation of the broke membrane isolated from human eyes with 0.5-2% ginseng extract for 24 hours, the hydraulic conductivity of the membrane increased (Table 2). (Fraction 2 in FIG. 8), a chloroform layer (Fraction 3 in FIG. 8), an ethyl acetate layer (Fraction 4 in FIG. 8) And there was little effect in the methanol layer (Fraction 1 in FIG. 8) and the butanol layer (Fraction 5 in FIG. 8). The most effective layer was the ginseng hot water extract (Fraction 7, p <0.001) and ginseng solvent extract final layer (fraction 6, Fig. 8, p <0.01) hydraulic conductivity.

Improvement of Hydraulic Conductivity of Bruce Membrane by Different Types of Solvents in Ginseng Extracts Fraction number
(Fig. 8) Concentration of fraction used
(Fraction concentration examined) Number of eye samples The ratio of hydraulic conductivity to base level
(Fold change in hydraulic conductivity over basal) valence
(Significance level) Control group - Culture 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

Improvement of hydraulic conductivity of Bruneian membrane by ginsenosides Rg1, Rb1 and compound K

The experiment was carried out in the same manner as in Example 3 except that the experimental group was cultured for 24 hours with ginsenoside and the transport was measured.

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

Improvement of hydraulic conductivity of Bruneian membrane by ginsenosides Rg1, Rb1 and compound K Concentration of fraction used
(Fraction concentration examined) Number of eye samples The ratio of hydraulic conductivity to base level
(Fold change in hydraulic conductivity over basal) valence
(Significance level) Control group  Culture in Tris-HCl 18 1.1 ± 0.2 - Compound K 190 [mu] g / ml 5 1.45 ± 0.15 P < 0.005 Rg1 200 [mu] g / ml One 1.2 - Rb1 200 [mu] g / ml One 1.27 -

Effect of Red Ginseng Extract on Hydraulic Conductivity of Bruch Membrane

The experiment was carried out in the same manner as in Example 3 except that the test group was cultured for 24 hours with 10% red ginseng extract and then transported.

After incubation with 10% red ginseng extract for 24 hours, the fluid conductivity of the membrane increased 2.2-fold (FIG. 3c) after the broke membrane isolated from human eyes (17 donors, ages 12-87). The results of the hydraulic conductivity and red ginseng extract cultures were expressed by logarithmic plots (Fig. 3d). Here transport showed exponential decline reduction with best-fit non-linear regression lines. Culture with red ginseng extract moves this curve upward (Fig. 3b), thereby increasing the age at which this curve meets the failure threshold. Hydraulic conductivity after red ginseng extract treatment gives 20-25 years younger. Thus, the red ginseng extract improves the hydraulic conductivity of the bruch membrane.

In addition, the hydraulic conductivities of the Bruneian membranes to the types of red ginseng (1: 2: Cheonjiyang, 3: Cheonggwanjang, 4: Goldsan Korean red ginseng gold) currently in circulation were measured by the same method as described above. As a result, the hydraulic conductivity of Bruch membranes was improved by the red ginseng extracts distributed. These results show that even when the extraction method of red ginseng extract is different, the hydraulic conductivity of the Bruch membrane is improved.

Effect of Red Ginseng Extract on Diffusion of Bruce Membrane

Bruce membrane was placed in the middle of the chamber using a Ussing chamber, and 0.1 mM FITC-albumin (MW 65 kDa, Tris-HCl as a solvent) was filled on the membrane side and Tris-HCl buffer was used on the other side. The diffusion function of the bruch membrane was measured by measuring the absorbance of the amount of FITC-albumin (MW 65 kDa) migrated at 490 nm after 12 hours of incubation at a concentration of 0.1 mM. (1) Hussain AA, Starita C, Hodgetts A, and Marshall J. (2010) Macromolecular characteristics of aging human Bruchmembrane: implications for age-related macular degeneration (AMD). Exp. Eye Res. 90: 703-710. (P <0.001, 33 donors, 12-92 years old) (Fig. 4c) when the cells were cultured with red ginseng extract. The baseline level of diffusion showed exponential decay with increasing age. The relationship between age, basal diffusion and diffusion after cultivation of red ginseng extract can be confirmed by a log graph (FIG. 4d). In the case of cultivation with red ginseng extract, the diffusion-age relationship curve is shifted upward and shows improvement of diffusion function. When cultured with red ginseng extract, the effect of diffusion is shown to be 16-21 years young. Thus, the red ginseng extract improves the diffusion function of the Bruch's membrane.

Effect of Red Ginseng Extract on MMP Enzyme Removed from Bruch Membrane

The aging of the bruch membrane leads to a greater amount of proteins trapped in the matrix of the membrane or to the membrane, degrading membrane transport. In particular, most of the high molecular weight MMP species present in association with the membrane (FIG. 2). This reduces the amount of free MMPs required for the activation process, and the reduction of activated MMP adversely affects the regeneration of the Bruch's membrane.

It was determined whether the combined form of MMP in the bruch membrane could be secreted into the perfusion of red ginseng extract (Fig. 5A). The human bruch membrane-choroid was separated and perfused for 30 h with Tris-HCl buffer to remove free-flowing components present in the bruch membrane. In the control group (1T-4T, sampling at intervals of 10 hours), most of the free MMP was secreted during the first harvest (1T) and decreased in amount over time. In the third harvest (3T) It did not exist. Thereafter, perfusion with 10% red ginseng extract resulted in secretion of most of the combined components described in the MMP pathway (FIG. 5A, 4G). Active MMP 2 and 9, which play important roles in the regeneration of the Brk membrane, were also secreted. Red ginseng secretes substances bound to the matrix, which improves the transport of the Bruch's membrane.

Effect of Red Ginseng Extract on Bruch Membrane

The aging of the bruch membrane leads to a greater amount of proteins trapped in the matrix of the membrane or to the membrane, degrading membrane transport. In the same manner as in Example 8, the human brain membrane-choroid was separated and perfused with a Tris-HCl buffer for 30 hours to remove free moving components present in the brain membrane. Thereafter, the amount of protein secreted after perfusion with 10% red ginseng extract was quantified by the Bradford assay (Fig. 5B). Red ginseng extract secreted proteins bound to the membrane, which helps to improve the transport of the membrane.

MMP secretion effect of RPE after treatment with red ginseng extract

After removal of the cornea, lens, and vitreous from the pig eyes, the retina is removed, and the eye cup is rinsed with phosphate buffered saline (PBS) buffer. Then, each incubation buffer is added, Time culture. (37 ° C, 5% CO 2) DMEM medium (Dulbecco Minimal Essential Medium), calf serum (fetal calf serum) and antibiotics were used as the basic medium. Thereafter, the solution was sampled to run a zymography gel capable of analyzing the amount of gelatinase. In the control medium, the pro-MMPs 2 and 9, and the active MMPs 2 and 9, are secreted continuously from the RPE (FIG. 7). When 10% red ginseng extract was cultured for 6 to 24 hours, the secretion of the precursor MMP9 (pro-MMP9) was increased but the secretion of active MMP9 was decreased. On the other hand, the secretion of pro and active MMP2 increased. HMW1 was also activated. The effect of these red ginseng extracts is helpful in the regeneration of Bruch's membrane.

Red ginseng extract was effective in increasing the secretion of active MMP2, a key enzyme in the regeneration process, which can improve the structural and functional parts of the Bruch's membrane.

MMP secretion effect of RPE of pig eyes after treatment with ginsenoside (Compound K, Rg1, Rb1)

The procedure of Example 10 was repeated. Compound K increased the amount of pro-MMP 2 and 9, and active MMP2, which would result in very useful results when compound K was added to red ginseng (FIG. 7). The amount of HMW1 activated after compound K treatment was increased. Rg1 increased the amount of pro-MMP9, which suggests 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 in the regeneration process that could improve the structural and functional parts of the Brk film.

Effect of Red Ginseng Extract on Lipid Removal of Bruch Membrane

Studies on the effects of increased deposition of lipid due to aging and the resulting transport of Bruch's membrane have been actively pursued. In order to remove the soluble substances in the human brain membrane-choroid, half of the sample was perfused with Tris-HCl buffer, and half of the sample was perfused with 10% red ginseng extract for 24 hours. Lipids extracted from the tissues in a volume ratio of 2: 1 with chloroform: methanol were separated by thin layer chromatography on Silica Gel plates. The reaction was carried out in a volume ratio of 50: 30: 8: 3 in half of the chloroform: methanol: acetic acid: water mixture and the heptane: diethyl ether: acetic acid acid was completed with a volume ratio of 70: 30: 2 and then stained with 0.2% amide black 10B. Cholesterol and two lipid substances are present in the sample obtained by perfusion with Tris-HCl. In the samples perfused with 10% red ginseng extract, no two lipids appeared upon cholesterol or Tris-HCl perfusion (FIG. 6). That is, from the cholesterol esters, triglycerides, cholesterol and other two lipid substances that appeared in the control group (T in FIG. 6), after perfusion with the red ginseng extract (G in FIG. 6) Cholesterol and the two lipid substances did not appear. Thus, red ginseng extract removes lipid substances from the membrane, which can help regenerate the membrane.

The following formulations are examples of constituent materials and dosages that can be used per day, and the present invention is not limited thereto.

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 mixed for the purpose of normally maintaining the retina function of a general person between 30 and 50 years old.

3. Formulation 2

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

However, in order to maintain retinal function normally, red ginseng extract or ginseng extract (1-3 g / day) and Rg1, Rb1, and compound K are mixed with a general person over 50 years old.

4. Formulation 3

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

However, in order to delay the onset and disease progression of patients who are at high risk for AMD and patients in the early stage of retinal disease, red ginseng extract or ginseng extract (2-4 g / day) and Rg1, Rb1, Compound K is mixed and used. It can be used as a pre-treatment for transplantation of stem cells or RPE cells for the treatment of macular degeneration (AMD). It improves the transport capacity of the Bruch's membrane prior to transplantation, improving the viability of the cells after transplantation and helping to make cell attachment better. It should be done 2-3 months before transplant. It can be used as a pre-treatment for patients undergoing micro-nano pulse laser therapy for the treatment of macular degeneration (AMD). Because the laser procedure differs in the results depending on the MMP response of RPE, combination 3, which helps RPE and Brake membranes, is used 2-3 months before.

5. Formulation 4

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

However, for the treatment of AMD, use of red ginseng extract or ginseng extract (3-6 g / day) is mixed with (a) Rg1, Rb1 and compound K, (b) daily recommended vitamins and minerals are added .

[Production Example 1]

Manufacture of tablets

The ginseng or red ginseng extract or ginsenoside Rg1, Rb1 and compound K were used to prepare tablets for oral administration by the wet granulation method and the dry granulation method with the following composition.

Composition: Ginseng extract, red ginseng extract, or at least one of ginsenosides Rg1, Rb1, and Compound K was selected as 200 mg, 10 mg of hard anhydrous silicic acid, 2 mg of magnesium stearate, 50 mg of microcrystalline cellulose, 25 mg of sodium starch glycolate , Lactose 101 mg, povidone 12 mg, and anhydrous ethanol.

[Production Example 2]

Injection preparation

An injection was prepared using ginseng or red ginseng extract or ginsenoside Rg1, Rb1 and compound K in the following composition.

Composition: One or more of ginseng extract, red ginseng extract, or ginsenoside Rg1, Rb1, and compound K was selected to obtain 100 mg, mannitol 180 mg, 25 mg of monohydrogenphosphate, 2974 mg of injectable purified water

[Production Example 3]

Manufacturing of beverages

* The following drinks were prepared using ginseng or red ginseng extract or ginsenosides Rg1, Rb1 and compound K as follows. Ginseng extract, red ginseng extract, or at least one of ginsenosides Rg1, Rb1 and Compound K, 200 mg of vitamin C, 75 mg of vitamin C, 4 mg of vitamin B2, 3 mg of vitamin B6, 1,000 mg of dietary fiber, 20000 mg of liquid fructose, 100 mg, and 50 mg of flavoring are mixed with purified water so that the volume becomes 50 ml. The mixture solution is filtered through a filter of 2 ~ 3 ㎛ and the final mixture is sterilized at 90 ~ 93 ℃ for 15 ~ 20 seconds, filled into 50 ml bottle and sterilized at 80 ~ 85 ℃ for 15 ~ 20 minutes. 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 substrate metalloproteinase
pro-MMP: a precursor matrix metalloprotease
active MMP: active matrix metalloprotease

Claims (38)

A pharmaceutical composition for preventing, delaying and treating a macular degenerative disease which comprises as an active ingredient a ginsenoside compound K (compound K). The pharmaceutical composition according to claim 1, wherein the active ingredient activates MMP (matrix metalloprotease) secretion from RPE (retinal pigment epithelium) cells. The pharmaceutical composition according to claim 1, wherein the active ingredient regenerates, maintains and improves the function of the Bruch's membrane. 4. The method of claim 3, wherein the active ingredient enhances the hydraulic conductivity of the Bruch membrane and improves the fluid transport function, thereby regenerating, maintaining and enhancing the function of the &lt; RTI ID = 0.0 &gt; A pharmaceutical composition for preventing, delaying and treating diseases. [4] The method of claim 3, wherein the effective ingredient improves the diffusion function of the Bruch's membrane, thereby activating the exchange of nutrients and waste materials between the RPE (retinal pigment epithelium) cells, the photoreceptor cells and the choroid, , Maintain and improve the macular degenerative diseases. The pharmaceutical composition according to claim 3, wherein the effective ingredient regenerates, maintains and improves the function of the Bruch's membrane by removing proteins trapped or bound in the matrix of the Bruch's membrane. Composition. 4. The method according to claim 3, wherein the active ingredient is selected from the group consisting of pro-matrix metalloprotease-2 (proMMP2) and proMMP9 (active matrix metalloprotease-2) active MMP9 (active matrix metalloprotease-9), thereby increasing the amount of free MMP (matrix metalloprotease) enzyme, which helps regenerate the damaged membrane, thereby regenerating, maintaining and improving the function of the Sublingual membrane And a pharmaceutically acceptable carrier, diluent or excipient. The pharmaceutical composition according to claim 3, wherein the active ingredient regenerates, maintains and improves the function of the Bruch's membrane by removing lipid components deposited on the Bruch's membrane. Composition. 4. The method of claim 3, wherein the active ingredient activates secretion of active matrix metalloprotease-2 (MMP2) from retinal pigment epithelium (RPE) cells, thereby regenerating, maintaining and improving the function of the Bruch's membrane Wherein the pharmaceutical composition is for preventing, delaying and treating macular degenerative diseases. The pharmaceutical composition for preventing, delaying and treating macular degeneration diseases according to claim 1, wherein the active ingredient further contains vitamins and minerals. A health functional food composition for preventing macular degeneration diseases, comprising a ginsenoside K (compound K) as an active ingredient. 12. The health functional food composition according to claim 11, wherein the active ingredient activates MMP (matrix metalloprotease) secretion from RPE (retinal pigment epithelium) cells. The health functional food composition according to claim 11, wherein the active ingredient regenerates, maintains and improves the function of the Bruch's membrane. 14. The method of claim 13, wherein the active ingredient enhances hydraulic conductivity of the Bruch membrane and improves fluid transport function, thereby regenerating, maintaining and enhancing the function of the &lt; RTI ID = 0.0 &gt; A health functional food composition for preventing diseases. 14. The method of claim 13, wherein the active ingredient improves the diffusion function of the Bruch's membrane Characterized in that the function of the Bruch's membrane is regenerated, maintained and improved by activating the exchange of nutrients and waste materials between the retinal pigment epithelium (RPE) cells, the photoreceptor cells and the choroid. 14. The method of claim 13, wherein the active ingredient is selected from the group consisting of pro-matrix metalloprotease-2 (proMMP2) and proMMP9 (active matrix metalloprotease-2) active MMP9 (active matrix metalloprotease-9), thereby increasing the amount of free MMP (matrix metalloprotease) enzyme, which helps regenerate the damaged membrane, thereby regenerating, maintaining and improving the function of the Sublingual membrane Wherein the composition comprises a physiologically acceptable salt thereof. 14. The health functional food composition for preventing macular degeneration diseases according to claim 13, wherein the effective ingredient regenerates, maintains and improves the function of the Bruch's membrane by removing proteins trapped or bound in the matrix of the Bruch's membrane. The health functional food composition for preventing macular degeneration diseases according to claim 13, wherein the effective ingredient regenerates, maintains and improves the function of the Bruch's membrane by removing lipid components deposited on the Bruch's membrane. 14. The method according to claim 13, wherein the active ingredient activates the secretion of active matrix metalloprotease-2 (MMP2) from retinal pigment epithelium (RPE) cells to regenerate, maintain and enhance the function of the MB membrane Or a pharmaceutically acceptable salt thereof. 12. The health functional food composition according to claim 11, wherein the effective ingredient comprises vitamins and minerals. A pharmaceutical composition for pretreating stem cells or retinal pigment epithelium (RPE) cells for the treatment of macular degeneration, which comprises the compound (K) as an active ingredient. A pharmaceutical composition for pre-treatment of a micro-nano pulsed laser for the treatment of macular degeneration characterized by comprising a ginsenoside compound (K) as an active ingredient. The present invention relates to a method for preventing and reducing retinal deterioration due to macular degeneration which regenerates, maintains and improves retinal functions by regenerating, maintaining and improving the function of the Bruch's membrane, which comprises the gentamicin compound K as an active ingredient. A pharmaceutical composition for therapeutic use. 24. The method of claim 23, wherein the active ingredient enhances hydraulic conductivity of the Bruch membrane and improves fluid transport function to regenerate, maintain and enhance the function of the Bruch membrane to regenerate and maintain retinal function And a method for preventing and treating retinal deterioration due to macular degeneration. 24. The method of claim 23, wherein the active ingredient is selected from the group consisting of macular degeneration that regenerates, maintains, and enhances the function of the Bruch membrane, thereby regenerating, maintaining, and improving retinal function by removing proteins trapped or bound in a matrix of the Bruch's membrane. A pharmaceutical composition for preventing and treating retinal deterioration. 24. The method according to claim 23, wherein the active ingredient improves the diffusion function of the Bruch's membrane, activating the exchange of nutrients and waste materials between the retinal pigment epithelium (RPE) cells, the photoreceptor cells and the choroid, The present invention relates to a pharmaceutical composition for preventing and treating retinal deterioration due to macular degeneration which regenerates, maintains and improves retinal function by regenerating, maintaining, and improving retinal function. 24. The method of claim 23, wherein the active ingredient is selected from the group consisting of proMMP2 (proM matrix metalloprotease-2) and proMMP9 (pro-matrix metalloprotease-9), active MMP2 (active matrix metalloprotease-2) It is known that active MMP9 (active matrix metalloprotease-9) is secreted, thereby increasing the amount of free MMP (matrix metalloprotease) enzyme and regenerating the damaged membrane. Therefore, A method for preventing and treating retinal deterioration due to macular degeneration, which regenerates, maintains, and improves retinal function. 24. The method of claim 23, wherein the active ingredient is selected from the group consisting of macular degeneration that regenerates, maintains, and enhances the retinal function by regenerating, maintaining and enhancing the function of the Bruch's membrane by removing lipid components deposited on the Bruch's membrane A pharmaceutical composition for preventing and treating retinal deterioration. 24. The method of claim 23, wherein the active ingredient activates the secretion of active matrix metalloprotease-2 (MMP2) from retinal pigment epithelium (RPE) cells to regenerate, maintain, and enhance the function of the Bruch's membrane, The present invention relates to a pharmaceutical composition for preventing and treating retinal deterioration due to macular degeneration which maintains and improves retinal function. 24. The method of claim 23, wherein the active ingredient is selected from the group consisting of retinal pigment epithelium (RPE) cells that activate MMP (matrix metalloprotease) secretion, regenerate, maintain, and enhance the function of the Bruch's membrane, For the prevention and treatment of retinal deterioration. A method for preventing retinal deterioration due to macular degeneration, which regenerates, maintains and improves retinal function by regenerating, maintaining and improving the function of the Bruch's membrane, which comprises the ginsenoside compound K (compound K) Health functional food composition. 32. The method of claim 31, wherein the active ingredient enhances hydraulic conductivity of the Bruch membrane and improves fluid transport function to regenerate, maintain and enhance the function of the Bruch membrane to regenerate and maintain retinal function And a composition for health functional food for preventing retinal deterioration due to macular degeneration. 32. The method of claim 31, wherein the active ingredient is selected from the group consisting of macular degeneration that regenerates, maintains, and enhances the function of the Bruch membrane, thereby regenerating, maintaining and enhancing retinal function by removing proteins trapped or bound in the matrix of the Bruch membrane. A health functional food composition for preventing retinal deterioration. 32. The method of claim 31, wherein the active ingredient enhances the diffusion function of the Bruch's membrane so as to activate the exchange of nutrients and waste materials between RPE (retinal pigment epithelium) cells, photoreceptor cells and choroid, Regenerating, maintaining, and improving retinal function, thereby preventing retinal deterioration due to macular degeneration. 32. The method of claim 31, wherein the active ingredient is selected from the group consisting of pro-matrix metalloprotease-2 (proMMP2) and proMMP9 (active matrix metalloprotease-2) It is known that active MMP9 (active matrix metalloprotease-9) is secreted, thereby increasing the amount of free MMP (matrix metalloprotease) enzyme and regenerating the damaged membrane. Therefore, Wherein the retinal deterioration is caused by macular degeneration that regenerates, maintains, and improves retinal function. 32. The method of claim 31, wherein the active ingredient is selected from the group consisting of macular degeneration that regenerates, maintains, and enhances the retinal function by regenerating, maintaining, and enhancing the function of the Bruch's membrane by removing lipid components deposited on the Bruch's membrane A health functional food composition for preventing retinal deterioration. 32. The method of claim 31, wherein the active ingredient activates secretion of active matrix metalloprotease-2 (MMP2) from retinal pigment epithelium (RPE) cells to regenerate, maintain, and enhance the function of the Bruch's membrane, A composition for the health functional food for preventing retinal deterioration due to macular degeneration which maintains and improves visual function. 32. The method of claim 31, wherein the active ingredient is selected from the group consisting of retinal pigment epithelium (RPE) cells, MMP (matrix metalloprotease) secretion, and the ability to regenerate, maintain, and enhance the Bruch's membrane to regenerate, To prevent deterioration of retinal function.

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