WO2018147663A1 - Composition comprenant un extrait composite de ginseng/ginseng rouge et de concombre de mer à titre de principe actif pour prévenir ou traiter une maladie liée à l'hypofonction de la membrane de bruch - Google Patents

Composition comprenant un extrait composite de ginseng/ginseng rouge et de concombre de mer à titre de principe actif pour prévenir ou traiter une maladie liée à l'hypofonction de la membrane de bruch Download PDF

Info

Publication number
WO2018147663A1
WO2018147663A1 PCT/KR2018/001722 KR2018001722W WO2018147663A1 WO 2018147663 A1 WO2018147663 A1 WO 2018147663A1 KR 2018001722 W KR2018001722 W KR 2018001722W WO 2018147663 A1 WO2018147663 A1 WO 2018147663A1
Authority
WO
WIPO (PCT)
Prior art keywords
membrane
bruch
ginseng
sea cucumber
extract
Prior art date
Application number
PCT/KR2018/001722
Other languages
English (en)
Korean (ko)
Inventor
이윤희
후세인알리
김대봉
Original Assignee
(주)알트리젠
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by (주)알트리젠 filed Critical (주)알트리젠
Priority to CA3052765A priority Critical patent/CA3052765C/fr
Priority to ES18751277T priority patent/ES2965670T3/es
Priority to EP18751277.7A priority patent/EP3586856B1/fr
Priority to CN201880010124.4A priority patent/CN110494148B/zh
Priority to JP2019565140A priority patent/JP6818913B2/ja
Priority to AU2018218588A priority patent/AU2018218588B2/en
Priority to US16/484,570 priority patent/US10940168B2/en
Priority claimed from KR1020180015887A external-priority patent/KR101893576B1/ko
Publication of WO2018147663A1 publication Critical patent/WO2018147663A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/616—Echinodermata, e.g. starfish, sea cucumbers or sea urchins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)

Definitions

  • the present invention relates to a composition for preventing or treating diseases related to Brueck's membrane deterioration, comprising ginseng / red ginseng and sea cucumber complex extract as an active ingredient, and more specifically, having an effect of regenerating the Bruk's membrane of the eye and improving transportation function. It relates to a composition for preventing, treating or ameliorating diseases associated with decreased Bruch's membrane function including ginseng / red ginseng and sea cucumber complex extract.
  • Ginseng is one of the traditional medicines used in the treatment of various diseases in Asian countries such as China, Korea and Japan.
  • Ginseng saponin ginsenoside
  • the main active ingredient of these ginseng has various physiological activities such as anti-aging, anti-inflammatory, antioxidant activity in the central nervous system and cardiovascular and immune system, antidiabetic activity and anti-tumor activity.
  • ginsenosides 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.
  • Sea cucumber is a general term of sea cucumbers belonging to the equatorial animal sea cucumber river, and it is the best supplement product called sea ginseng because it contains a large amount of medicinal ingredients such as saponin.
  • Sea cucumber is a medicine that has been used for a long time in China and the East. It has excellent effects on diabetes, asthma, etc., and it is a medicine that can regain energy when you lose energy and collapse due to sweating due to temperature increase in summer.
  • sea cucumbers have a remarkable resilience effect that when the part of the body is cut, the cut site returns to its original state in three months, and new intestines are formed in one month even if the intestines are removed. Enhance phagocytosis of the phagocytes to boost the immune function and is known to be effective in the treatment of wounds.
  • Eye cells are light-sensitive cells in the retina that transmit information to the brain during visual processes, allowing objects to be recognized. Eye cells are the most active part of our body's metabolism, and effective nutrient delivery and waste removal are essential. Due to the nature of an environment rich in essential fatty acids, light and high levels of oxygen, much of the damage is caused by free radicals. In this case, retinal pigment epithelium (RPE) can be used to continuously regenerate the outer segments of damaged cells.
  • RPE retinal pigment epithelium
  • Eye cells and RPE are supplied with nutrients through the choroid blood circulation. If nutrients from the blood are secreted from the capillaries of the choroid, they must first pass through the extracellular matrix Bruch's membrane before reaching the RPE and the cell. Nutrients such as small glucose, oxygen, and amino acids pass through the Bruch's membrane with simple passive diffusion, and vitamins, trace metals, and lipids bind to the carrier protein and then pass through the Bruch's membrane to the RPE. Are separated. In contrast, waste products from the cells and RPE pass through the Bruch's membrane and are removed from the choroid. Most waste products are toxic and can potentially damage the Brueck's membrane and trigger inflammatory reactions. Therefore, the efficient mass transport ability of the Bruch's membrane can be seen as a prerequisite for maintaining normal visual acuity and survival of visual cells (FIG. 1).
  • Aging increases the thickness of the Brueck membrane by two to three times, reducing the diffusion gradients in which nutrients and waste are exchanged, making it difficult to spread the material in the Brueck membrane. This results in deposition of lipids and proteo-lipid complexes and waste products discarded in RPE on membranes, increased cross-linking of collagen and increased amounts of denatured collagen.
  • glycosylation increases protein and lipid glycosides (AGE; advanced protein glycation end-products, ALE; advanced lipid glycation end-products) (Handa et al. 1999), and damaged or polymerized proteins. Deposition of complexes also increases.
  • thiols in the free state are reduced because thiol groups exposed to normal or denatured proteins due to aging are trapped in the membrane as they form dimers or polymers through oxidation. All these changes result in disruption of the membrane's transport capacity and adversely affect nutrient delivery and waste removal (Holz et al. 1994) (Fig. 2).
  • ARDS age-related eye disease study
  • US-related macular degeneration study a US-related macular degeneration study that has been conducted for more than 10 years, has not yet demonstrated the effectiveness of a composition consisting of vitamin and mineral additives (Kassof et al. 2001).
  • the ideal solution to macular degeneration and vision damage due to aging is to facilitate the transport of Brueck's membrane, so that all the necessary nutrients in the plasma are supplied.
  • the inventors of the present application have made diligent efforts to develop a therapeutic method that can solve the root cause of eye deterioration due to aging, including age-related macular degeneration.
  • the present invention was completed by finding out that the regenerating effect is excellent and confirming that it can be used as a composition for the prevention or treatment of diseases caused by a decrease in the function of Bruk's membrane.
  • Bok D Retinal photoreceptor-pigment epithelium interactions. Friedenwald Lecture. Invest. Ophthalmol. Vis. Sci. 1985; 26: 1659-94.
  • MMP matrix metalloproteinase pathway in both age-related macular degeneration (AMD) and Alzheimer's disease (AD). J. Neurodegenerative diseases (in Press).
  • An object of the present invention is a complex extract of ginseng and sea cucumber or fractions thereof; Or it provides a pharmaceutical composition for the prevention, delay or treatment of Bruch's membrane function-related diseases including a complex extract of red ginseng and sea cucumber or fractions thereof as an active ingredient.
  • Another object of the present invention is a complex extract of ginseng and sea cucumber or fractions thereof; Or to provide a health functional food composition for the prevention, delay or improvement of Bruch's membrane (function) related to the functional degradation related to red ginseng and sea cucumber complex extract or fractions thereof as an active ingredient.
  • Another object of the present invention is a complex extract of ginseng and sea cucumber or fractions thereof; Or to provide a health functional food composition for improving eye health comprising a red ginseng and sea cucumber complex extract or fractions thereof as an active ingredient.
  • Another object of the present invention is a complex extract of red ginseng and sea cucumber or fractions thereof; Or it provides a method for preventing, delaying or treating a disease related to Brueck's membrane deterioration comprising administering to a subject a composition comprising a complex extract of ginseng and sea cucumber or a fraction thereof as an active ingredient.
  • the present invention is to solve the above problems, a complex extract of ginseng and sea cucumber or fractions thereof; Or it provides a pharmaceutical composition for the prevention, delay or treatment of Bruch's membrane function-related diseases, including a complex extract of red ginseng and sea cucumber or fractions thereof as an active ingredient.
  • ginseng used in the present invention is Korean ginseng ( Panax ginseng ), hoegisam ( P. quiquefolius ), Jeonchisam ( P. notoginseng ), bamboo shoots ( P. japonicus ), trifolium ginseng ( P. trifolium ), Himalayan ginseng ( P. pseudoginseng ), vietnamese ginseng ( P. vietnamensis ), and American ginseng ( P. quinquefolium ).
  • red ginseng of the present invention is prepared by heating the ginseng through steam or sun-dried, preferably steam, more preferably steamed ginseng at 98 ⁇ 100 °C, dried ginseng around 60 °C do.
  • the present invention is described as being applied to ginseng or red ginseng extract, but can be applied to all ginseng processed in various forms, such as ginseng, rice ginseng, white ginseng, taegeuk ginseng, black ginseng, purified ginseng, enzyme-treated ginseng, fermented ginseng and fermented red ginseng It is not limited thereto.
  • sea cucumber used in the present invention refers to marine invertebrates belonging to Phylum Echinodermata Class Holothuroidea, scale sea cucumber, Hwamun sea cucumber, multifoot ring sea cucumber, Orthodox sea cucumbers, Monakari sea cucumbers, Snake-eye black sea cucumbers, Sea cucumbers, etc. belonging to the Order Aspidochirotida, etc. ) May include, but is not limited to, white sea cucumbers, ginseng sea cucumbers, and the like.
  • the sea cucumber is recommended as a health food for high blood pressure, arteriosclerosis, diabetic and obese patients, but it is recommended for the use of rejuvenation and tonics, pregnant women and women with weak physical condition. There is no bar.
  • extract used in the present invention is an extract obtained by the extraction process of ginseng / red ginseng or sea cucumber, dried product obtained by drying the ginseng, red ginseng or sea cucumber, dilution or concentrate of the extract, dried product obtained by drying the extract, And extracts of all formulations that can be formed using the extract itself and the extract, such as modifiers and purified products of the extract, or mixtures thereof.
  • the extract or fraction of the present invention may preferably be used in liquid form after extraction.
  • the method of extracting the ginseng / red ginseng and sea ginseng is not particularly limited, and may be extracted according to methods commonly used in the art.
  • the type of extraction solvent used to extract the ginseng / red ginseng and sea ginseng is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the extraction solvent include water, alcohols or mixed solvents thereof, and when using alcohol as the solvent, preferably C1 to C4 alcohol, more preferably C1 to C2 lower alcohol More preferably, 80% ethanol aqueous solution may be used, but is not limited thereto.
  • the sea cucumber extract of the present invention may preferably be water or ethanol extract.
  • the hot water extraction method when extracting the ginseng / red ginseng and sea cucumber by the hot water extraction method, it is preferable to extract once to five times, more preferably three times to extract repeatedly, but is not limited thereto.
  • the extraction solvent may be added 0.1 to 100 times the weight of the dried ginseng / red ginseng and sea cucumber, preferably 0.3 to 5 times.
  • Extraction temperature is preferably 20 °C to 130 °C but is not limited thereto.
  • the extraction time is preferably 30 minutes to 48 hours, but is not limited thereto.
  • the vacuum concentration is preferably a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto.
  • the drying is preferably natural drying, hot air drying, freeze drying, vacuum drying, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited to any method known in the art to remove moisture. .
  • the skin and gut of the sea cucumber can be extracted or dried as a whole, and the skin and gut of the sea cucumber can be separated or dried separately, respectively, and the skin and gut extract or dried It may be used or may be mixed.
  • red ginseng was prepared by first drying at 60-70 ° C. for 12-20 hours, and then sun-dried, hot water over 4 times using water as a solvent. After extraction, the resultant was filtered, cooled, centrifuged, purified, and concentrated in vacuo to obtain an extract.
  • the dried sea cucumber is ground to prepare a sea cucumber powder, 70% ethanol is added thereto as an extraction solvent, and extracted for about 3 to 6 hours, and ethanol is removed in a vacuum state. To obtain an extract.
  • fraction refers to the result obtained by performing fractionation to separate a specific component or a specific group of components from a mixture comprising several different components.
  • the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art.
  • Non-limiting examples of the fractionation method is a method of obtaining a fraction from the extract by treating the extract obtained by extracting ginseng / red ginseng and sea cucumbers with a predetermined solvent.
  • the kind of the fractionation solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the fractionation solvents include polar solvents such as water and alcohols; Nonpolar solvents, such as hexane, ethyl acetate, chloroform, dichloromethane, etc. are mentioned. These may be used alone or in combination of two or more thereof.
  • alcohols of C1 to C4 may be preferably used.
  • the active ingredient of the present invention has an effect of preventing the onset of the disease, delaying the progress of the disease, or treating the disease related to the decrease of the Bruk's membrane function by improving the transport function of the Bruk's membrane.
  • the active ingredient of the present invention is transported by improving the hydraulic conductivity of the Brueck membrane, improving the diffusion function of the Brueck membrane, or removing proteins or lipids bound or trapped in the Brueck membrane. You can improve the function.
  • the active ingredient of the present invention can prevent the onset of the disease, delay the progression of the disease, or treat the disease by which the Bruch membrane is reduced by improving the Brux membrane function.
  • the active ingredient of the present invention can regenerate the Brueck membrane and improve the Brueck membrane function by removing the high molecular weight complex (HMW) or lipid component bound or deposited on the Brueck membrane.
  • HMW high molecular weight complex
  • the active ingredient of the present invention can regenerate the Brooke membrane and improve the Brooke membrane function by secreting pro-MMP2, pro-MMP9, active MMP2 and active MMP9 from the matrix of the Brooke membrane.
  • the active ingredient of the present invention can regenerate the Bruch's membrane by activating the active MMP secretion from retinal epithelial cells (RPE), and improve the Bruch's membrane function.
  • RPE retinal epithelial cells
  • the complex extract of ginseng / red ginseng and sea cucumber of the present invention is polymerized on the Bruch membrane to degrade the substances that degrade the Bruch membrane, and decomposes the substances, which are trapped in the matrix of the Brux membrane, or nutrients such as proteins or lipids bound together. Secretions and waste products help nourish the eyes and release waste products.
  • prevention or “delay” refers to any action that inhibits or delays the onset of a disease resulting from a decreased function of the Bruch's membrane by administering the composition of the invention to a subject.
  • treatment refers to any action by which the composition of the present invention is administered to a subject so that the symptoms of a disease resulting from a decreased function of the Bruch's membrane improve or benefit.
  • improvement means any action that at least reduces the parameters associated with the condition being treated, such as the extent of symptoms.
  • the complex extract of ginseng / red ginseng and sea cucumber or fractions thereof may be contained in an amount of preferably 0.1 wt% to 99.99 wt% based on the total weight of the pharmaceutical composition, More preferably, it may be contained in 10% by weight to 99.99% by weight, and more preferably 50% by weight to 99.99% by weight.
  • the effect of improving the transport function of the Brux membrane, the Brux membrane regeneration and the Brux membrane function improvement according to the complex extract or fractions thereof of the ginseng / red ginseng and sea cucumber is fully exhibited to achieve the object of the present invention There is an advantage.
  • the pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier, in addition to containing the complex extract or fractions thereof of the ginseng / red ginseng and sea cucumber as an active ingredient.
  • the "pharmaceutically acceptable” means that it is commonly used in the pharmaceutical field that does not impede the biological activity and properties of the compound to be administered without stimulating the organism upon administration thereof.
  • the pharmaceutical composition of the present invention may be formulated with the carrier, and may be utilized as food, medicine, feed additives, drinking water additives, and the like.
  • the type of the carrier is not particularly limited and any carrier can be used as long as it is commonly used in the art.
  • Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, maltodextrin, glycerol, ethanol, and the like. Can be. These may be used alone or in combination of two or more thereof.
  • composition of the present invention may be used by adding other pharmaceutically acceptable additives, such as excipients, diluents, antioxidants, buffers or bacteriostatic agents, if necessary, fillers, extenders, wetting agents, disintegrants, dispersants, interfaces Active agents, binders, lubricants, and the like may be additionally added and used.
  • additives such as excipients, diluents, antioxidants, buffers or bacteriostatic agents, if necessary, fillers, extenders, wetting agents, disintegrants, dispersants, interfaces Active agents, binders, lubricants, and the like may be additionally added and used.
  • compositions of the present invention can be formulated and used in a variety of formulations suitable for oral or parenteral administration.
  • suitable for oral administration include troches, lozenges, tablets, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups or elixirs, and the like. Can be mentioned.
  • a binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose (Cellulose) or gelatin (Gelatin) and the like; Excipients such as Dicalcium phosphate and the like; Disintegrants such as corn starch or sweet potato starch; Lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate, or polyethylene glycol wax can be used, and sweeteners, fragrances, and syrups can also be used. Can be.
  • a liquid carrier such as fatty oil may be additionally used in addition to the above-mentioned materials.
  • Non-limiting examples of the parenteral preparations include injection liquids, suppositories, respiratory inhalation powders, spray aerosols, ointments, application powders, oils, creams, and the like.
  • a sterile aqueous solution In order to formulate the pharmaceutical composition for parenteral administration, a sterile aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a freeze-dried preparation, an external preparation, and the like may be used.
  • the non-aqueous solvent and the suspension may be propylene glycol, Polyethyleneglycol, vegetable oils such as olive oil, injectable esters such as ethyloleate and the like can be used.
  • the pharmaceutical composition of the present invention when the pharmaceutical composition of the present invention is formulated into an injection solution, the composition of the present invention is mixed with water with a stabilizer or buffer to prepare a solution or suspension, which is then used as an ampoule or vial. It can be formulated for unit administration of.
  • a propellant or the like when the pharmaceutical composition of the present invention is formulated with an aerosol, a propellant or the like may be combined with the additive to disperse the dispersed concentrate or the wet powder.
  • composition of the present invention when formulated into an ointment, a cream, etc., animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, oxidation It can be formulated using zinc etc. as a carrier.
  • a pharmaceutically effective amount, effective dosage of the pharmaceutical composition of the present invention may vary depending on the method of formulation, the mode of administration, the time of administration and / or route of administration, and the like, to achieve by administering the pharmaceutical composition.
  • the type and extent of the response, type of subject, age, weight, general state of health, condition or extent of the disease, sex, diet, excretion, drug used concurrently or simultaneously with the individual And various similar factors well known in the medical arts, and those skilled in the art can readily determine and prescribe a dosage effective for the desired treatment.
  • the dosage for the more preferred effect of the pharmaceutical composition of the present invention may be preferably 0.01 mg / kg to 1,000 mg / kg, more preferably 1 mg / kg to 500 mg / kg per day.
  • Administration of the pharmaceutical composition of the present invention may be administered once a day, may be divided into several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
  • the route of administration and mode of administration of the pharmaceutical composition of the present invention may be independent of each other, and are not particularly limited in the way, and any route of administration and administration as long as the pharmaceutical composition can reach the desired site of interest. You can follow the way.
  • the pharmaceutical composition may be administered by oral or parenteral administration.
  • parenteral administration method for example, intravenous administration, intraperitoneal administration, intramuscular administration, transdermal administration or subcutaneous administration may be used, and the method of applying, spraying or inhaling the composition to a diseased site may also be used. May be, but is not limited to these.
  • the pharmaceutical composition of the present invention may be preferably administered orally or transdermally.
  • the composition of the present invention is one selected from the group consisting of amino acids, antioxidants, vitamins, minerals, metals, lutein, astaxanthin, zeaxanthin and bilberry extract in order to enhance the prevention, delay or treatment effect of Bruch's membrane-related diseases It may further comprise the above composition. More specifically, the vitamin or mineral may be vitamin C, vitamin E, beta carotene, zinc oxide, and cupric oxide, which are effective for improving eye function, but are not limited thereto.
  • the Bruch's membrane deterioration-related diseases include age-related macular degeneration (AMD), Sorsby's fundus dystrophy, ML (Malattia Levintanese), Stargardt disease (Stargardt disease), Best yolk-shaped macular dystrophy (Best's) vitelliform retinal dystrophy) or Doyne's honeycomb retinal dystrophy (DHRD), but is not limited thereto.
  • AMD age-related macular degeneration
  • Sorsby's fundus dystrophy ML (Malattia Levintanese)
  • Stargardt disease Stargardt disease
  • Best yolk-shaped macular dystrophy Best's vitelliform retinal dystrophy
  • DHRD Doyne's honeycomb retinal dystrophy
  • the present invention is a complex extract of the ginseng and sea cucumber or fractions thereof; Or it provides a health functional food composition for the prevention, delay or improvement of Bruch's membrane function-related diseases including a complex extract of red ginseng and sea cucumber or fractions thereof as an active ingredient.
  • the present invention is a complex extract of the ginseng and sea cucumber or fractions thereof; Or it provides a health functional food composition for improving eye health comprising a red ginseng and sea cucumber complex extract or fractions thereof as an active ingredient.
  • the complex extract of ginseng / red ginseng and sea cucumber or fractions thereof, and the efficacy thereof are the same as described above in connection with the pharmaceutical composition of the present invention.
  • the health functional food composition of the present invention When used as a food additive, the composition may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the kind of the food is not particularly limited, and includes all foods in a general sense.
  • foods that can be added to the material include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, dairy products, including other noodles, gums, ice cream, various soups, drinks, tea , A drink, an alcoholic beverage, and a vitamin complex.
  • the health functional food composition of the present invention when the health functional food composition of the present invention is a beverage composition, it may contain various flavors or natural carbohydrates and the like as an additional ingredient, as in a conventional beverage.
  • the natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweeteners such as dextrin, cyclodextrin; Synthetic sweeteners such as saccharin and aspartame; and the like.
  • the proportion of the additional components added above may be appropriately determined by the choice of those skilled in the art.
  • the nutraceutical composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin , Alcohols, carbonation agents used in carbonated beverages, and the like.
  • the health functional food composition of the present invention may contain a flesh for preparing natural fruit juice, fruit drink or vegetable drink. These components can be used independently or can be used in combination of 2 or more. The proportion of such additives may also be appropriately selected by those skilled in the art.
  • the present invention is a complex extract of red ginseng and sea cucumber or fractions thereof; Or it provides a method for preventing, delaying or treating a disease related to Brueck's membrane deterioration comprising administering to a subject a composition comprising a complex extract of ginseng and sea cucumber or a fraction thereof as an active ingredient.
  • the composite composition according to the present invention has the effect of slowing or reversing the aging process of the eye by improving the transport function of the Brueck membrane, removing lipid components deposited on the membrane, and promoting the regeneration of the Brueck membrane, thereby causing age-related macular lesions. It is excellent in preventing or treating various diseases caused by deterioration of the Bruch's membrane due to aging, including sex (AMD), and due to reduced transport of vitamins, metals and antioxidants, which are issued due to the maintenance of public health and aging. You can solve the problem.
  • FIG. 1 is a diagram illustrating the cross-sectional image of the human retina and the components of phototransduction.
  • Figure 2 is a graph showing the structural changes of the Bruk's membrane due to aging, (A) the thickness of the Bruk's membrane increases by two to three times with age, (B) the accumulation of damaged or denatured collagen, and (C ) Major lipid substances, such as cholesterol esters, increase exponentially, and (D) free thiol groups decrease, causing aggregation of proteins.
  • FIG. 3 is a diagram showing the change of Bruch's membrane due to aging and the rapid change in macular degeneration patients.
  • Figure 4 shows the mechanism of MMP action that plays a role in aging and regeneration of the Bruch's membrane and abnormal MMP action mechanism in macular degeneration patients.
  • Figure 6 shows the change in the degree of diffusion of the Bruk's membrane in humans due to aging of the general population and macular degeneration patients.
  • Figure 7 is a result showing the effect of improving the transport function of Bruk's membrane of (A) red ginseng extract and (B) sea cucumber extract of the present invention.
  • Figure 8 is a result showing the effect of improving the repair conductivity of the Brueck membrane by repeated treatment of the red ginseng extract according to an embodiment of the present invention.
  • 11 is a dose response curve showing the lipid secretion effect from the Bruch membrane of the red ginseng extract and sea cucumber extract of the present invention.
  • Fig. 13 shows the result of removing free MMP enzyme from human Bruch's membrane.
  • 17 is a result showing the synergistic effect of the improvement of the Bruch membrane transport function of ginseng and sea cucumber complex extract.
  • MMP is a proteolytic enzyme that is secreted in the form of an inactive precursor (pro-form) from the RPE to the Bruch's membrane.
  • the small peptides are removed from these precursors, resulting in activated MMP2 and active MMP9.
  • Activated MMP2 and MMP9 enzymes can degrade most of the substances that make up the extracellular matrix through the activation process, removing the damaged components and replacing them with new ones.
  • the mechanism of regeneration of the membrane plays a role in maintaining the structure and function of the Brooke membrane in a healthy state.
  • pro-MMP2 and pro-MMP9 form a high molecular weight complexes (HMW) called HMW1 and HMW2 in the Bruch membrane through a polymerization reaction.
  • HMW1 and HMW2 high molecular weight complexes
  • LMMCs large macromolecular complexes
  • the macular and peripheral areas of central vision were examined in the eyes of 56 healthy subjects in the range of 1 to 96 years and the eyes of 11 patients with macular degeneration. ) And their effects were evaluated.
  • the hydraulic conductivity of the Brueck membrane separated from the donated eye was measured to confirm the transport capacity of the waste.
  • the separated Bruch membrane was placed in an open Ussing chamber (Ussing chamber) to measure the quantitative change of the fluid under hydrostatic pressure to calculate the change in hydraulic conductivity (FIG. 5B, C).
  • the fluid transport capacity of the macular section decreased exponentially as aging progressed, and the transport capacity decreased by half every 16 years (FIG. 5D).
  • the data in FIG. 5D is shown by converting the exponential decay linearly using a semi-log plot on the Y axis.
  • the Bruch's membrane requires a minimum hydraulic conductivity function, which is indicated by a failure line.
  • This functional threshold can be determined by dividing the amount of fluid transported by the RPE by the hydrostatic pressure of the Brueck membrane.
  • the hydraulic conductivity of the Brueck membrane required to deliver the RPE fluid can be calculated from the equation below.
  • Hydraulic Conductivity (HC) fluid flow / pressure
  • the degree of diffusion decreases slowly compared to the macula part (FIG. 6E), but in the case of macular degeneration, it was confirmed to decrease very rapidly (see black circle and red line of FIG. 6E).
  • the function of the macular part of the macular degeneration patient can be measured as compared with the degree of reduction of the peripheral part, it can be confirmed that the degree is much more rapid and rapid than the peripheral part.
  • An object of the present invention is to improve the transport capacity of the Brueck membrane in the general elderly population and macular degeneration patients. This is done by removing the waste present in the membrane and reactivating the decomposition system on the membrane.
  • water, spirits, and a mixture of water and alcohol may be selected and extracted.
  • water was extracted in 5 to 10 times the weight of raw ginseng for 12 hours at 80 ⁇ 85 °C
  • the extraction was carried out for 3 hours
  • the third extraction was carried out with water 5 to 10 times the weight of raw ginseng and extracted for 8 hours at 80 to 85 ° C.
  • the fourth extraction was carried out with water 5 to 10 times the weight of raw ginseng. Extraction was performed at 85 ° C. for 8 hours. Thereafter, the foreign matter was removed by filtration, cooled to 10 to 15 ° C., purified by centrifugation, and concentrated in vacuo to prepare a red ginseng extract for use in the present invention.
  • Dried sea cucumber was used to prepare sea cucumber powder using a grinder, and 70% ethanol was added thereto, followed by extraction for about 3 to 6 hours. Removing ethanol in a vacuum to prepare a sea cucumber extract used in the embodiment of the present invention.
  • the Bruch membrane is placed in an open-type Ussing chamber and passed through the Tris-HCl buffer under hydrostatic pressure through a tube, and after a certain time, the solution passed through the fluid transport (fluid transport) Was measured.
  • the experimental group was treated with red ginseng extract by concentration of 0 to 10% or sea cucumber extract by concentration of 0 to 10%, and the fluid transport was measured again after incubation for 24 hours.
  • the graph shows the fold change of the reaction by extract concentration against the basal hydraulic conductivity measured before the reaction.
  • both red ginseng and sea cucumber extract showed hyperbolic dose-response curves (hyperbolic dose-response curves) it was found that the hydraulic conductivity for the membrane is improved as the dose is increased.
  • red ginseng extract In saturation state, the hydraulic conductivity of red ginseng extract was increased by about 3 times and sea cucumber extract by about 3.2 times compared with that of no addition of each extract. It has been confirmed that it can have a significant effect on the improvement of transportation function.
  • Example 3 the same method as in Example 3 was used, but only Tris-HCl was used as a control, and the experimental group was treated with 2.5% red ginseng extract, respectively. After the first culture, the fluid transport was measured, and further treated with 2.5% red ginseng extract, followed by incubation for 24 hours, and then the second measurement was performed.
  • the red ginseng extract prepared in Examples 1 and 2 and the sea cucumber extract and the mixture was tested by the method of Example 3 using the Bruk membrane of the eyes of 12-89 year old eye donors to confirm the effect of improving the Bruch's membrane repair conductivity .
  • the Bruch's membrane isolated from the eyes of 38 eye donors (12-89 years old) was incubated with 10% red ginseng extract for 24 hours, and Tris-HCl was used as a control.
  • red ginseng extract and the sea cucumber extract improved the hydraulic conductivity of the Bruch's membrane in a similar manner (red ginseng: 2.15 ⁇ 0.33 times increased, sea cucumber: 2.13 ⁇ 0.47 times increased, Mean ⁇ SD). Increased 2.89 ⁇ 0.58 fold. From this, it was confirmed that there was a statistically significant improvement effect when the complex extract was treated compared to a single extract (p ⁇ 0.001, Mean ⁇ SD).
  • the improvement of the hydraulic conductivity of the red ginseng and sea cucumber extracts is the same as the effect that makes the Bruch membrane about 20 to 25 years young. This improvement in repair conductivity prevents the eye from going below the fail threshold, thereby reducing the risk of pathological progression such as macular degeneration or preventing vision deterioration due to aging.
  • the main components of the lipid waste of the Bruch's membrane are cholesterol esters, cholesterol, triglycerides and phospholipids. Dose-response experiments were conducted to determine whether red ginseng extracts and sea cucumber extracts were effective in removing lipid extracts accumulated on Bruch's membrane.
  • FIGS. 11 and 12 dose response curves of various types of lipid secretion, lipid secretion data, and kinetics are shown in FIGS. 11 and 12.
  • FIG. 11 when incubated with the red ginseng extract and the sea cucumber extract, the cholesterol esters, cholesterol, triglycerides and phospholipids deposited on the Bruch's membrane were secreted to remove various types of lipids from the membrane. Both extracts were found to reach saturation with maximum effect at a concentration of about 2.5%.
  • Fig. 12A the lipid secretion data
  • Fig. 12B secretion effect
  • the MMP enzyme of the Bruch's membrane exists in free form or bound to the membrane.
  • MMP bound to the membrane was first identified in the separated Bruch's membrane.
  • the separated Bruch membrane was placed in an open Ussing chamber to flow through the Tris-HCl buffer to remove free materials.
  • the fluid passing through the membrane was measured every hour and the amount of secreted MMP was confirmed by gelatin zymography.
  • a Bruch membrane of 6 mm in diameter was cut out to measure the MMP content.
  • Free MMPs were removed within 1 hour after the start of perfusion, and then slowly secreted to remove almost all free MMPs within 5 hours of perfusion (FIG. 13). Once the free MMP was released from the membrane, the Bruch membrane was separated from the chamber and the remaining MMP was extracted using the SDS buffer. Soluble or freely present MMP material was secreted slowly between 5 and 12 hours of perfusion, but most MMPs in the Bruch's membrane are removed after 5 to 12 hours of perfusion because they remain bound or trapped in the membrane. It could be confirmed that it remained on the membrane without being.
  • sea cucumber extract had a similar MMP secretion effect as red ginseng extract, and was particularly effective in removing a large amount of HMW2 bound to the membrane.
  • the combination of red ginseng and sea cucumber extract (RG + SC) showed a much better effect on the removal of MMP bound to the membrane than red ginseng or sea cucumber alone extract, confirming the synergistic effect of the complex.
  • the complex of red ginseng and sea cucumber extract is the most effective for the removal of MMP enzyme trapped in the membrane, the combination of the extract acts to secrete a large molecular weight compound bound or trapped on the membrane to transport the Brueck membrane It's a great way to improve your skills.
  • the removal of activated MMP2 and MMP9 can help normalize the membrane secretion system, which has the effect of degrading abnormal proteins, which aids in the regeneration of the Brueck membrane.
  • the enhanced porosity of the Brueck membrane, together with the new MMPs released by RPE is expected to play an even more efficient role in the recovery and degradation of the Brueck membrane.
  • Example 8 Human eye using red ginseng and sea cucumber extract Brooke On pellet Present MMP Secretion effect of enzyme
  • the Bruk's membrane of human eyes separated from two eyes of a 75-year-old donor was used.
  • MMP enzymes were trapped or bound in the membrane.
  • a certain volume of pellets were incubated with Tris-HCl buffer as a control, and the experimental group was incubated with 2.5% red ginseng extract or 2.5% sea cucumber extract. After incubation at 37 ° C. for 24 hours, centrifugation was performed to determine the amount of MMP secreted into the supernatant and the MMPs that remained bound to the pellets.
  • the activated MMP2 and MMP9 were secreted slightly in the control group, and in the case of HMW2, most of them remained bound to the pellets.
  • the red ginseng extract treated some secreted enzyme, but HMW2 still remained in the membrane, similar to the control.
  • the sea cucumber extract was treated, most of the HMW2 was secreted, and the activated forms of HMW1, MMP2 and MMP9 were also secreted. From this, it was found that sea cucumber extracts can activate HMW1 in the activated state and pro-MMP2 and pro-MMP9 in the precursor state from the membrane to remove wastes in the Bruch's membrane, which may have a positive effect on improving transport function.
  • the treatment strategy proposed in the present invention is to improve the material transport ability due to aging as shown in Figure 16 to increase the straight line upwards.
  • a 1.5-fold improvement in hydraulic conductivity would make the Bruchmak's function nine years younger, and a four-fold improvement in hydraulic conductivity would improve the donor's eye function for 32 years.
  • the degree of improvement can be determined according to the age group targeted for treatment. For the general population who do not yet have visual ailments, lower doses can help maintain eye health, while older people can use higher doses to prevent aging and the associated disorders of Brueck's function. In patients with signs of eye disease due to aging, much higher doses can be used to delay or treat the progression of the disease.
  • ginseng extract and sea cucumber extract improved the hydraulic conductivity of the Bruch's membrane in a similar manner (Ginseng: 1.81 ⁇ 0.18 times increased, Sea cucumber: 2.32 ⁇ 0.05 times increased, Mean ⁇ SD). 3.58 ⁇ 0.65 fold increase. From this, it was confirmed that there was a statistically significant improvement effect when the composite extract was treated compared to a single extract (p ⁇ 0.05, Mean ⁇ SD).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Food Science & Technology (AREA)
  • Botany (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Biotechnology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition comprenant un extrait composite de concombre de mer et ginseng/ginseng rouge à titre de principe efficace, destinée à prévenir et à traiter une maladie liée à la dysfonction de la membrane de Bruch et, notamment, une composition destinée à prévenir et à traiter une maladie liée à la dysfonction de la membrane de Bruch, où la composition comprend un extrait composite de concombre de mer et ginseng/ginseng rouge qui a pour effet de régénérer la membrane de Bruch de l'œil et d'améliorer la fonction de transport de la membrane de Bruch. La composition composite selon la présente invention améliore la fonction de transport de la membrane de Bruch et élimine les lipides qui se sont accumulés sur la membrane pour favoriser ainsi la régénération de la membrane de Bruch, et avoir pour effet de retarder ou d'inverser le processus de sénescence de l'œil. De plus, la composition est très utile dans la prévention ou le traitement de diverses maladies attribuées à une réduction de la fonction de la membrane de Bruch avec l'âge, dont la dégénérescence maculaire liée à l'âge (DMLA) et peut résoudre le problème associé au maintien de la santé oculaire chez les personnes normales et à la réduction du transport, résultant de la sénescence, de vitamines, de métaux et de substances anti-oxydantes.
PCT/KR2018/001722 2017-02-09 2018-02-08 Composition comprenant un extrait composite de ginseng/ginseng rouge et de concombre de mer à titre de principe actif pour prévenir ou traiter une maladie liée à l'hypofonction de la membrane de bruch WO2018147663A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
CA3052765A CA3052765C (fr) 2017-02-09 2018-02-08 Composition comprenant un extrait composite de ginseng/ginseng rouge et de concombre de mer a titre de principe actif pour prevenir ou traiter une maladie liee a l'hypofonction de la membrane de bruch
ES18751277T ES2965670T3 (es) 2017-02-09 2018-02-08 Composición que comprende extracto compuesto de ginseng/ginseng rojo y pepino de mar como ingrediente eficaz para prevenir o tratar la enfermedad relacionada con la hipofunción de la membrana de Bruch
EP18751277.7A EP3586856B1 (fr) 2017-02-09 2018-02-08 Composition comprenant un extrait composite de ginseng/ginseng rouge et de concombre de mer à titre de principe actif pour prévenir ou traiter une maladie liée à l'hypofonction de la membrane de bruch
CN201880010124.4A CN110494148B (zh) 2017-02-09 2018-02-08 人参/红参及海参复合提取物作为有效成分的布鲁赫膜功能下降相关疾病预防或治疗用组合物
JP2019565140A JP6818913B2 (ja) 2017-02-09 2018-02-08 人参／紅参及びナマコ複合抽出物を有効成分とするブルッフ膜機能の低下関連病気の予防又は治療用組成物
AU2018218588A AU2018218588B2 (en) 2017-02-09 2018-02-08 Composition comprising composite extract from ginseng/red ginseng and sea cucumber as effective ingredient for preventing or treating bruch's membrane hypofunction-related disease
US16/484,570 US10940168B2 (en) 2017-02-09 2018-02-08 Method of treating Bruch's membrane hypofunction disease

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20170018196 2017-02-09
KR10-2017-0018196 2017-02-09
KR10-2018-0015887 2018-02-08
KR1020180015887A KR101893576B1 (ko) 2017-02-09 2018-02-08 인삼/홍삼 및 해삼 복합 추출물을 유효성분으로 하는 브루크막 기능 저하 관련 질병 예방 또는 치료용 조성물

Publications (1)

Publication Number Publication Date
WO2018147663A1 true WO2018147663A1 (fr) 2018-08-16

Family

ID=63106899

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2018/001722 WO2018147663A1 (fr) 2017-02-09 2018-02-08 Composition comprenant un extrait composite de ginseng/ginseng rouge et de concombre de mer à titre de principe actif pour prévenir ou traiter une maladie liée à l'hypofonction de la membrane de bruch

Country Status (1)

Country Link
WO (1) WO2018147663A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000029009A1 (fr) * 1998-11-18 2000-05-25 Coastside Bio Resources Peptides presentant une activite anticancereuse et anti-inflammatoire
KR20090123195A (ko) * 2008-05-27 2009-12-02 메타볼랩(주) 시력 개선용 조성물
KR20140045260A (ko) * 2013-05-06 2014-04-16 농업회사법인 주식회사 지바이오믹스 인삼추출물에 의한 망막 재생을 통한 눈 기능 저하 및 황반 변성 질환의 예방 및 치료용 조성물

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000029009A1 (fr) * 1998-11-18 2000-05-25 Coastside Bio Resources Peptides presentant une activite anticancereuse et anti-inflammatoire
KR20090123195A (ko) * 2008-05-27 2009-12-02 메타볼랩(주) 시력 개선용 조성물
KR20140045260A (ko) * 2013-05-06 2014-04-16 농업회사법인 주식회사 지바이오믹스 인삼추출물에 의한 망막 재생을 통한 눈 기능 저하 및 황반 변성 질환의 예방 및 치료용 조성물

Non-Patent Citations (34)

* Cited by examiner, † Cited by third party
Title
BIRD ACMARSHALL J: "Retinal pigment epithelial detachments in the elderly", TRANS. SOC. OPHTHAL. UK, vol. 105, 1986, pages 674 - 682
BIRKEDAL-HANSEN HMOORE WGBODDEN MKWINDSOR LJBIRKENDAL-HANSEN BDECARLO AENGLER JA: "Matrix metalloproteinases: a review", CRIT. REV. ORAL BIOL. MED., vol. 4, 1993, pages 197 - 250, XP002049986
BOK D: "Retinal photoreceptor-pigment epithelium interactions. Friedenwald Lecture", INVEST. OPHTHALMOL. VIS. SCI., vol. 26, 1985, pages 1659 - 94
BUI BVKALLONIATIS MVINGRYS AJ: "The contribution of glycolytic and oxidative pathways to retinal photoreceptor function", INVEST. OPHTHALMOL. VIS. SCI, vol. 44, 2003, pages 2707 - 2715
CHIHARA ENAO-I N: "Resorption of subretinal fluid by transepithelial flow of the retinal pigment epithelium", GRAEFES ARCH KLIN EXP OPHTHALMOL., vol. 223, 1985, pages 202 - 204
EMI KPEDERSON JETORIS CB: "Hydrostatic pressure of the suprachoroidal space", INVEST. OPHTHALMOL. VIS. SCI., vol. 30, 1989, pages 233 - 238
ESTERBAUER HSCHAUR RJZOLLNER H: "Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes", FREE RADIC. BIOL. MED., vol. 11, 1991, pages 81 - 128, XP023523401, doi:10.1016/0891-5849(91)90192-6
FRAMBACH DAMARMOR MF: "The rate and route of fluid resorption from the subretinal space of the rabbit", INVEST. OPHTHALMOL. VIS. SCI., vol. 22, 1982, pages 292 - 302
GUO LHUSSAIN AALIMB GAMARSHALL J: "Age-dependent variation in the metalloproteinase activity of Bruch's membrane and choroid", INVEST. OPHTHALMOL. VIS. SCI., vol. 40, 1999, pages 2676 - 2682
HANDA JTVERZIJL NMATSUNAGA HAOTAKI-KEEN ALUTTY GAKOPPELE JMMIYATA THJELMELAND LM: "Increase in the advanced glycation end-product pentosidine in Bruch's membrane with age", INVEST. OPHTHALMOL. VIS. SCI., vol. 40, 1999, pages 775 - 779
HOLZ FGSHERAIDAH GSPAULEIKHOFF DBIRD AC: "Analysis of lipid deposits extracted from human macular and peripheral Bruch's membrane", ARCH. OPHTHALMOL., vol. 112, 1994, pages 402 - 406
HOSOKAWA, M. ET AL.: "Bio-functions of Marine Carotenoids", FOOD SCIENCE AND BIOTECHNOLOGY, vol. 18, no. 1, 2009, pages 1 - 11, XP009516138 *
HUGHES BAMILLER SSMACHEN TE: "The effects of cAMP on fluid absorption and ion transport across frog retinal pigment epithelium: measurements in the open-circuit state", J. GENE PHYSIOL., vol. 83, 1984, pages 875 - 899
HUSSAIN AALEE YMARSHALL J: "High molecular weight gelatinase species of human Bruch's membrane: compositional analyses and age-related changes", INVEST. OPHTHALMOL. VIS. SCI., vol. 51, 2010, pages 2363 - 71
HUSSAIN AALEE YZHANG JJFRANCIS PTMARSHALL J: "Disturbed matrix metalloproteinase (MMP) pathway in both age-related macular degeneration (AMD) and Alzheimer's disease (AD", J. NEURODEGENERATIVE DISEASES, 2016
HUSSAIN AALEE YZHANG JJMARSHALL J: "Disturbed matrix metalloproteinase activity of Bruch's membrane in age-related macular degeneration (AMD", INVEST. OPHTHALMOL. VIS. SCI., vol. 52, 2011, pages 4459 - 66
HUSSAIN AAROWE LMARSHALL J: "Age-related alterations in the diffusional transport of amino acids across the human Bruch's-choroid complex", JOURNAL OF THE OPTICAL SOCIETY OF AMERICA, A, OPTICS, IMAGE SCIENCE, & VISION, vol. 19, no. 1, 2002, pages 166 - 72
HUSSAIN AASTARITA CHODGETTS AMARSHALL J: "Macromolecular characteristics of ageing human Bruch's membrane: implications for age-related macular degeneration (AMD", EXP. EYE RES., vol. 90, 2010, pages 703 - 710, XP027051367
HUSSAIN AASTARITA CMARSHALL J: "Focus on Macular Degeneration Research", 2004, NOVA SCIENCE PUBLISHERS, INC., article "Transport characteristics of ageing human Bruch's membrane: Implications for AMD", pages: 59 - 113
KARWATOWSKI WSSJEFFERIES TEDUANCE VCALBON JBAILEY AJEASTY DL: "Preparation of Bruch's membrane and analysis of the age related changes in the structural collagens", BRIT. J. OPHTHALMOL., vol. 79, 1995, pages 944 - 952
KASSOF AKASSOFF JBUEHLER 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., vol. 119, 2001, pages 1417 - 36
KUMAR AEL-OSTA AHUSSAIN AAMARSHALL J: "Increased sequestration of matrix metalloproteinases in ageing human Bruch's membrane: implications for ECM turnover", INVEST. OPHTHALMOL. VIS. SCI., vol. 51, 2010, pages 2664 - 70
LEE YHUSSAIN AASEOKJ-HKIM S-HMARSHALL J: "Modulating the transport characteristics of Bruch's membrane with steroidal glycosides and its relevance to age-related macular degeneration (AMD", INVEST. OPHTHALMOL. VIS SCI., vol. 56, no. 13, 2015, pages 8403 - 18, XP055533604, doi:10.1167/iovs.15-16936
LEE, Y. ET AL.: "Modulating the Transport Characteristics of Bruch's Membrane with Steroidal Glycosides and Its Relevance to Age-related Macular Degeneration (AKAD", INVENSTIGATIVE OPHTHALMOLOGY AND VISUCAL SCIENCE, vol. 56, no. 13, 2015, pages 8403 - 8418, XP0055533604 *
MAURICE DMSALMON JZAUBERMAN H: "Subretinal pressure and retinal adhesion", EXP. EYE RES., vol. 12, 1971, pages 212 - 217, XP022969096, doi:10.1016/0014-4835(71)90093-5
MOORE DJHUSSAIN AAMARSHALL J: "Age-related variation in the hydraulic conductivity of Bruch's membrane", INVEST. OPHTHALMOL. VIS. SCI., vol. 36, no. 7, 1995, pages 1290 - 7
OWSLEY CJACKSON GRWHITE MFEIST REDWARDS D: "Delays in rod mediated dark adaptation in early age-related maculopathy", OPHTHALMOL., vol. 108, 2001, pages 1196 - 1202
OWSLEY CMCGWIN GJACKSON GRHEINBURGER DCPIYATHILAKE CJKLEIN RWHITE MFKALLIES K: "Effect of short term, high-dose retinol on dark adaptation in age and age-related maculopathy", INVEST. OPHTHALMOL. VIS. SCI., vol. 47, no. 4, 2006, pages 1310 - 8
RAMRATTEN RSVAN DER SCHAFT TLMOOY CMDE BRUIJN WCMULDER PGHDE JONG PTVM: "Morphometric analysis of Bruch's membrane, the choriocapillaris and the choroid in ageing", INVEST. OPHTHALMOL. VIS. SCI., vol. 35, 1994, pages 2857 - 2864
SAKAI NDECATUR JNAKANISHI KELDRED GE: "Ocular age pigment 'A2E': an unprecedented pyridinium bisretinoid", JAM. CHEM. SOC., vol. 118, 1996, pages 1559 - 1560
See also references of EP3586856A4 *
STEINMETZ RLHAIMOVICI RJUBB CFITZKE FWBIRD A: "Symptomatic abnormalities of dark adaptation in patients with age-related Bruch's membrane change", BR. J. OPHTHALMOL., vol. 77, 1993, pages 549 - 554
TSUBOI SPEDERSON JE: "Effect of plasma osmolality and intraocular pressure on fluid movement across the blood-retinal barrier", INVEST. OPHTHALMOL. VIS. SCI., vol. 29, 1988, pages 1747 - 1749
WITZ G: "Biological interactions of a,b-unsaturated aldehydes", FREE RADIC. BIOL. MED., vol. 7, 1989, pages 333 - 349, XP023523312, doi:10.1016/0891-5849(89)90137-8

Similar Documents

Publication Publication Date Title
CN110494148B (zh) 人参/红参及海参复合提取物作为有效成分的布鲁赫膜功能下降相关疾病预防或治疗用组合物
KR101314215B1 (ko) 진세노사이드 알비원에 의한 망막 재생을 통한 눈 기능 저하 및 건성 황반 변성 질환의 예방 및 치료용 조성물
KR102111372B1 (ko) 해삼 추출물을 유효성분으로 하는 브루크막 기능 저하 관련 질병 예방 및 치료용 조성물
KR101449469B1 (ko) 홍삼추출물에 의한 망막 재생을 통한 눈 기능 저하 및 황반 변성 질환의 예방 및 치료용 조성물
WO2013141581A1 (fr) Composition pharmaceutique ou aliment naturel comprenant des extraits de fruit de lonicera coerulea var. edulis en tant que principes actifs dans la prévention ou l'amélioration de maladies vasculaires cérébrales ischémiques
WO2016093613A2 (fr) Composition pour la prévention ou le traitement d'une perte de poids anormale, contenant un extrait de pelure de mandarine satsuma
KR20140045260A (ko) 인삼추출물에 의한 망막 재생을 통한 눈 기능 저하 및 황반 변성 질환의 예방 및 치료용 조성물
KR101539573B1 (ko) 진세노사이드 화합물 K (compound K)에 의한 망막 재생을 통한 눈 기능 저하 및 황반 변성 질환의 예방 및 치료용 조성물
WO2018147663A1 (fr) Composition comprenant un extrait composite de ginseng/ginseng rouge et de concombre de mer à titre de principe actif pour prévenir ou traiter une maladie liée à l'hypofonction de la membrane de bruch
WO2018117572A1 (fr) Composition comprenant de l'extrait de concombre de mer comme ingrédient efficace pour prévenir et traiter la maladie liée au dysfonctionnement de la membrane de bruch
WO2015160181A1 (fr) Composition pour la prévention ou le traitement d'hyperplasie de cellule de muscle lisse vasculaire et de troubles de migration ou de troubles de prolifération endothéliale vasculaire, comprenant un extrait de dendropanax morbifera
WO2018080157A1 (fr) Composition pour la prévention, le soulagement ou le traitement d'un déficit cognitif, contenant un extrait de ficus erecta en tant que principe actif
WO2020004989A1 (fr) Composition pour la prévention, l'amélioration ou le traitement de la cachexie comprenant du kimchi
WO2018190638A1 (fr) Composition pour la prévention ou le traitement de maladies cornéennes, contenant un extrait de glycine max
WO2013051904A9 (fr) Composition de prévention et traitement de la détérioration de la vision et de dégénérescence maculaire liée à l'âge par réparation rétinienne à l'aide d'extraits de ginseng/ginseng rouge et de ginsénoside
KR101539574B1 (ko) 진세노사이드 Rg1에 의한 망막 재생을 통한 눈 기능 저하 및 황반 변성 질환의 예방 및 치료용 조성물
WO2024090941A1 (fr) Composition de prévention, d'atténuation ou de traitement d'une maladie du segment antérieur de l'œil, comprenant comme principe actif un extrait végétal du genre aloe
WO2022216107A1 (fr) Composition anticancéreuse comprenant un extrait d'elaeocarpus sylvestris ou un produit purifié de celui-ci en tant que principe actif
WO2023033535A1 (fr) Composition comprenant un extrait de marron d'inde
WO2024219856A1 (fr) Composition pour prévenir, améliorer ou traiter des maladies oculaires
WO2023182757A1 (fr) Composition pour prévenir et traiter un accident vasculaire cérébral
WO2023022390A1 (fr) Composition de prévention des lésions oculaires contenant un extrait de dendropanax morbifera lev.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18751277

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 3052765

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2019565140

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2018218588

Country of ref document: AU

Date of ref document: 20180208

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2018751277

Country of ref document: EP

Effective date: 20190909