WO2017142306A1 - Composition pharmaceutique pour prévenir ou traiter les maladies dégénératives du cerveau, contenant un polysaccharide extracellulaire produit par ceriporia lacerata en tant que principe actif - Google Patents

Composition pharmaceutique pour prévenir ou traiter les maladies dégénératives du cerveau, contenant un polysaccharide extracellulaire produit par ceriporia lacerata en tant que principe actif Download PDF

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WO2017142306A1
WO2017142306A1 PCT/KR2017/001651 KR2017001651W WO2017142306A1 WO 2017142306 A1 WO2017142306 A1 WO 2017142306A1 KR 2017001651 W KR2017001651 W KR 2017001651W WO 2017142306 A1 WO2017142306 A1 WO 2017142306A1
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extracellular polysaccharide
degenerative brain
pharmaceutical composition
mycelium culture
culture medium
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PCT/KR2017/001651
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English (en)
Korean (ko)
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김윤수
유혜동
김용환
최진우
신은지
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㈜퓨젠바이오파마
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    • 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
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus

Definitions

  • the present invention is an active ingredient produced by Ceriporia lacerata ( Ceriporia lacerata ), the mycelium culture medium of the Ceriporia laccerata containing the active ingredient, the dry powder of the mycelia culture medium, or the extract of the mycelium culture medium effective It relates to a pharmaceutical composition for the prevention or treatment of degenerative brain disease containing as a component.
  • Dementia is a gradual deterioration of memory and cognitive abilities to the extent that it impairs daily life, and can be classified into vascular dementia and Alzheimer's dementia.
  • vascular dementia cerebral infarction or stroke occurs mainly due to blood clots formed in blood vessels, and it is known that brain cells around the affected area are damaged to cause symptoms such as memory loss.
  • Alzheimer's disease which accounts for much more than vascular dementia, progresses slowly with symptoms such as memory loss, personality changes, and decreased thinking ability, but most patients die of pneumonia within 8 to 10 years. It is known.
  • Recent epidemiologic studies have reported that risk factors for cerebrovascular diseases, such as hypertension, diabetes, hyperlipidemia, and heart disease, increase the incidence of Alzheimer's as well as vascular dementia, but the exact etiology and treatments are unknown. .
  • Characteristic lesions of Alzheimer's dementia include amyloid plaques, which include beta-amyloid, and neurofibrillary tangles, which are formed in the brain tissue, causing inflammation of immune cells, and Ca 2. In addition to destroying the + channel, it has been reported to reduce the amount of the neurotransmitter, acetylcholine, causing memory and cognitive decline.
  • drugs capable of blocking beta-amyloid production in the brain or eliminating insoluble beta-amyloid aggregates are useful as therapeutic agents for Alzheimer's dementia (Hardy J. & Selkoe DJ, Science 297: 353-6, 2002; Singer O.
  • FDA US Food and Drug Administration
  • Ceriporia laccerata is a type of white fungus, and is known to perform co-metabolism called lignin decomposition in order to use carbon sources such as cellulose, hemicellulose, other polysaccharides, and glycerol in an ecosystem.
  • Ceriporia laccerata only the use of Ceriporia laccerata culture extract in Korean Patent No. 10-1031605, filed by the present inventors, is known. The effect of preventing or treating degenerative brain diseases using liporia lacserata has not been reported.
  • the active ingredient produced by Seriphoria laccerata the mycelium culture medium of the Seriphoria laccerata containing the active ingredient, the dry powder of the mycelium culture medium, or the extract of the mycelium culture medium degenerative brain disease
  • the present invention has been completed by confirming that the prophylactic or therapeutic effect is exhibited.
  • Another object of the present invention is to provide a dietary supplement for the prevention or improvement of degenerative brain diseases containing the active ingredient produced by Ceriporia laccerata.
  • Still another object of the present invention is to provide a method for preventing or treating degenerative brain disease using an active ingredient produced by Ceriporia laccerata.
  • Another object of the present invention is to provide a use of the active ingredient produced by Ceriporia laccerata for use in the preparation of a pharmaceutical composition for the prevention or treatment of degenerative brain disease.
  • the present invention is an extracellular polysaccharide produced by Ceriporia lacerata ( Ceriporia lacerata ), mycelium culture medium of the seriporia laccerata comprising the extracellular polysaccharide, dry powder of the mycelia culture medium It provides a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, or containing the extract of the mycelia culture medium as an active ingredient.
  • the present invention is an extracellular polysaccharide produced by Ceriporia lacerata ( Ceriporia lacerata ), mycelium culture medium of the seriporia laccerata containing the extracellular polysaccharide, the mycelium culture solution
  • Ceriporia lacerata Ceriporia lacerata
  • mycelium culture medium of the seriporia laccerata containing the extracellular polysaccharide
  • the mycelium culture solution Provided is a dietary supplement for the prevention or improvement of degenerative brain disease, containing a powder or an extract of the mycelium culture medium as an active ingredient.
  • the present invention is an extracellular polysaccharide produced by Ceriporia lacerata ( Ceriporia lacerata ), mycelium culture medium of the three cells, including the extracellular polysaccharide, mycelium culture medium
  • a method for preventing or treating degenerative brain disease comprising administering a dry powder or an extract of the mycelium culture to a subject in need thereof.
  • the present invention is an extracellular polysaccharide produced by Ceriporia lacerata , the extracellular for use in the manufacture of a pharmaceutical composition for the prevention or treatment of degenerative brain disease
  • the present invention provides a use of the mycelium culture medium of the seriporia laccerata containing the polysaccharide, the dry powder of the mycelium culture medium, or the extract of the mycelium culture medium.
  • Extracellular polysaccharide produced by Seriphoria laccerata according to the present invention the mycelium culture medium of the Seriporia laccerata containing the extracellular polysaccharide, the dry powder of the mycelium culture medium, or the extract of the mycelium culture medium active ingredient
  • 1 is a graph showing the long-term memory improvement effect of the extracellular polysaccharide produced by Seriphoria lac serrata.
  • Figure 2 is a graph showing the short-term memory improvement effect of the extracellular polysaccharide produced by Seriporia lacserata.
  • Figure 3 is a graph showing the effect of improving the final memory capacity of the extracellular polysaccharide produced by Seriporia lacserata.
  • Figure 4 is a graph showing the effect of improving the learning ability of the extracellular polysaccharide produced by Seriporia lacserata.
  • Figure 5 is a graph showing the effect of improving the balance of the extracellular polysaccharide produced by Seriporia lac serrata.
  • Figure 6 is a graph showing the change in acetylcholine content by the treatment of the extracellular polysaccharide produced by Seriporia lacserata.
  • Figure 7 is a graph showing the effect of inhibiting the acetylcholine esterase activity by the treatment of the extracellular polysaccharide produced by Ceriporia lacserata.
  • the present invention is an extracellular polysaccharide produced by Ceriporia lacerata ( Ceriporia lacerata ), mycelium culture medium of the seriporia laccerata comprising the extracellular polysaccharide, the dry powder of the mycelium culture medium, or the extract of the mycelium culture solution It provides a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, containing as an active ingredient.
  • extracellular polysaccharide is a part of the cell wall of a microorganism such as a fungus, and the polysaccharide is secreted to the outside of the cell to form a capillary around it or secreted into the periphery or medium as a slime. Means.
  • the extracellular polysaccharide is secreted by the microorganism to protect itself from the external environment such as antibodies, toxic substances, protozoa and bacteriophage.
  • the extracellular polysaccharide is 40 to 60% by weight sugar and 30 to 40% by weight protein, 40 to 50% by weight sugar and 32 to 38% by weight protein, 43 to 47% by weight sugar and 33 to 36% by weight Protein, or about 45% by weight sugar and about 34% by weight protein.
  • the sugar may contain mannose, galactose and glucose.
  • the extracellular polysaccharide may have a molecular weight of 100 to 150 kDa, 110 to 140 kDa or 115 to 125 kDa, and more specifically may have a molecular weight of about 120 kDa.
  • the extracellular polysaccharide comprises the steps of: (a) liquid culture of the Ceriporia laccerata mycelium to prepare a Ceriporia laccerata mycelium culture solution; (b) drying and powdering the Ceriporia laccerata mycelium culture solution; And (c) extracting the Ceriporia laccerata mycelium culture powder with a solvent, filtering the same, and concentrating under reduced pressure.
  • the medium for the liquid culture of the seriporia laccerata mycelium in the step (a) is sugar, glucose, starch, hydrate, soybean meal, soybean meal, magnesium sulfate (MgSO 4 ), potassium phosphate (KH 2 PO 4 ), potassium diphosphate (K 2 HPO 4 ) and water, and the hydrogen ion concentration (pH) may be 4.5 to 6.0.
  • the medium is 0.2 to 3% by weight of sugar, 0.2 to 3% by weight of glucose, 0.2 to 4% by weight of starch, 0.1 to 0.5% by weight of water, 0.1 to 0.5% by weight of wheat flour, 0.2 to 3% of soy flour %, 0.05 to 0.1 wt% magnesium sulfate (MgSO 4 ), 0.05 to 0.25 wt% potassium monophosphate (KH 2 PO 4 ), 0.05 to 0.25 wt% potassium phosphate (K 2 HPO 4 ) and the balance of water Can be.
  • MgSO 4 magnesium sulfate
  • KH 2 PO 4 potassium monophosphate
  • K 2 HPO 4 potassium phosphate
  • the liquid culturing in step (a) may be performed under a blue LED light source, and specifically, the liquid culturing may be performed by maintaining a concentration of carbon dioxide at 1,000 to 2,000 ppm under a blue LED light source.
  • the liquid culture for example, at 20 to 28 °C, hydrogen ion concentration of 4.5 to 6.0, light source to maintain a blue LED, illuminance of 0.1 to 0.8 LUX and air is injected at 0.5 to 2.0 kgf / cm2,
  • the concentration may be performed for 8 to 13 days while maintaining at 1,000 to 2,000 ppm. Specifically, it may be performed for 5 to 15 days at the conditions of 20 to 25 °C, pH 4.5 to 6.0, 0.5 to 2.0 kgf / cm2 of air injection and 1,000 to 2,000 ppm carbon dioxide concentration.
  • the content of the extracellular polysaccharide produced is high.
  • the parent strain of step (a) maintains a constant temperature of about 25 ° C. in a shaker incubator using a PDB (potato dextrose broth) medium in a conical flask with a good strain stored at 1 to 5 ° C. in a PDA (potato dextrose agar) medium. And can be used after 7 to 9 days incubation process.
  • the culture solution or the obtained mycelium can be used as the inoculum.
  • the amount of mycelia to be added to the inoculum is preferably about 0.5% (w / v) based on the amount of the solution to be cultured.
  • the amount of extracellular polysaccharides does not increase as the amount of mycelia (% / 100 ml, w / v) increases, so the medium composition has the highest content of extracellular polysaccharides, not the best nutritional ratio and environmental conditions for the growth of mycelia. It is preferable to apply the selective culture conditions to form.
  • the culture solution can be separated and purified into a mycelium and an aqueous solution.
  • the separation and purification may be performed by repeatedly purifying a solution obtained by removing the mycelium by a centrifuge with a multi-sheet filter press and a vibration centrifugal separator (PALLSEP), and then irradiating ultraviolet (UV) light for 1 minute. have.
  • the culture solution may be sealed and stored after removing the oxygen, which may bring a change in the content of the active ingredient due to the growth of the mycelia when the mycelium is present in the culture solution.
  • step (b) the mycelia culture solution prepared in step (a) may be dried and powdered.
  • the drying may be performed for 48 to 96 hours at a temperature of 40 °C or less, more specifically 30 °C or less to prevent the disappearance of the active material.
  • the drying of step (b) is preferable to use a vacuum freeze dryer rather than a vacuum dryer that sets the evaporation temperature relatively high because the change in the effective substance content is minimized.
  • step (c) after extracting the dry powder of the mycelia culture solution obtained in step (b) with a solvent, the extracellular polysaccharide which is the active ingredient of the composition according to the present invention is separated.
  • distilled water 100 ml of distilled water is added to 3 to 10 g of the dry powder of the mycelium culture medium, followed by well suspension, followed by centrifugation at 5,000 to 10,000 rpm for 10 to 30 minutes to obtain a supernatant. After adding three times the extraction solvent, it can be placed in a refrigerator at 1 to 5 ° C and allowed to stand for 10 to 15 hours. After only centrifuging the supernatant again at 5,000 to 10,000 rpm for 10 to 30 minutes in the stationary material, the precipitate may be recovered to prepare a crude extracellular polysaccharide. The crude extracellular polysaccharide can be vacuum-dried at 30 ° C. or lower to obtain extracellular polysaccharide.
  • the extraction solvent may be a solvent selected from the group consisting of water, lower alcohols having 1 to 4 carbon atoms, acetone, ether, chloroform and ethyl acetate or a mixed solvent thereof, and more specifically, water, methanol, ethanol, butanol , Acetone and ethyl acetate may be a solvent selected from the group consisting of, or a mixed solvent thereof, more preferably, water or 50 to 99% (v / v) of ethanol aqueous solution.
  • the pharmaceutical composition for preventing or treating degenerative brain disease may be an extracellular polysaccharide produced by Seriphoria laccerata, a mycelium culture medium of Seriphoria laccerata containing the extracellular polysaccharide, a dry powder of the mycelium culture medium, or In addition to including the extract of the mycelium culture medium as an active ingredient, a carrier, excipient, and diluent may be further included.
  • the extracellular polysaccharide may be included in 0.1 to 80% by weight, or 0.1 to 50% by weight relative to the total weight of the pharmaceutical composition for the prevention or treatment of degenerative brain diseases, mycelium culture medium of Seriporia laccerata, dry powder thereof or the mycelia.
  • the extract of the culture solution may be appropriately included in an amount corresponding to the content of the extracellular polysaccharide.
  • the effective amount of the extracellular polysaccharide, the culture solution containing the same, the dry powder of the culture solution, or the extract of the culture solution may be appropriately adjusted according to the method of use and purpose of the pharmaceutical composition.
  • compositions according to the invention can each be formulated and used according to conventional methods. Suitable formulations include, but are not limited to, tablets, pills, powders, granules, dragees, hard or soft capsules, solutions, suspensions or emulsions, injections, suppositories, and the like.
  • compositions according to the invention can be prepared in suitable formulations using pharmaceutically inert organic or inorganic carriers. That is, when the formulation is a tablet, coated tablet, dragee and hard capsule, it may include lactose, sucrose, starch or derivatives thereof, talc, calcium carbonate, gelatin, stearic acid or salts thereof. In addition, when the formulation is a soft capsule, it may include polyols of vegetable oils, waxes, fats, semisolids and liquids. Furthermore, when the formulation is in the form of a solution or syrup, it may include water, polyols, glycerol, and / or vegetable oils and the like.
  • the pharmaceutical composition according to the present invention may further include a preservative, a stabilizer, a humectant, an emulsifier, a solubilizer, a sweetener, a colorant, an osmotic agent, an antioxidant, and the like, in addition to the carrier.
  • the method of administering the pharmaceutical composition according to the present invention can be easily selected according to the dosage form, and can be administered orally or parenterally.
  • the dosage may vary depending on the age, sex, weight, severity, and route of administration of the patient, but is generally 5 to 1,000 mg / kg body weight based on the extracellular polysaccharide, which is an active ingredient, specifically 10 to 600
  • the amount of mg / kg body weight may be administered once to three times a day.
  • the above dosage does not limit the scope of the present invention.
  • the pharmaceutical composition according to the present invention may not only provide an excellent prophylactic or therapeutic effect on degenerative brain disease, but also have little toxicity and side effects due to the drug, so that the pharmaceutical composition may be used safely even for long-term administration for the purpose of preventing or treating degenerative brain disease. .
  • the extracellular polysaccharide of the present invention exhibited short-term and long-term memory recovery effect.
  • the effect of improving the learning ability, balance sensory effect, increased acetylcholine content and inhibition of acetylcholine esterase activity of the extracellular polysaccharide of the present invention showed the effect of treating degenerative brain disease.
  • the extracellular polysaccharide according to the present invention exhibits a prophylactic and therapeutic effect of degenerative brain disease, and the mycelium culture medium of Seriphoria laccerata containing the extracellular polysaccharide, the dry powder of the mycelium culture medium, and the mycelium culture medium. The extract also shows the same effect.
  • the pharmaceutical compositions of the present invention can be used in various degenerative brain diseases, such as dementia (eg, senile dementia, frontal lobe dementia, cerebrovascular dementia, Lewy body dementia, etc.), Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, It can be used for the prevention and treatment of diseases selected from the group consisting of Pick disease, Creutzfeld-Jakob disease and combinations thereof.
  • dementia eg, senile dementia, frontal lobe dementia, cerebrovascular dementia, Lewy body dementia, etc.
  • Alzheimer's disease eg., Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease
  • diseases selected from the group consisting of Pick disease, Creutzfeld-Jakob disease and combinations thereof.
  • the present invention is an extracellular polysaccharide produced by Ceriporia lacerata ( Ceriporia lacerata ), mycelium culture medium of the seriporia laccerata comprising the extracellular polysaccharide, dry powder of the mycelium culture medium, or the mycelia culture medium It provides a functional food for the prevention or improvement of degenerative brain disease, containing the extract as an active ingredient.
  • the health functional food according to the present invention may be in the form of powder, granules, tablets, capsules or beverages, and may be candy, chocolate, gum, tea, vitamin complexes, health supplements, and the like.
  • the content of the extracellular polysaccharide according to the present invention contained in the health functional food, mycelium culture medium containing the same, the dry powder of the mycelium culture medium, or the extract of the mycelium culture medium usually 0.01 to 50 weight of the total food weight %, Or 0.1 to 20% by weight.
  • a health beverage composition it may be included in an amount of 0.02 to 10 g, or 0.3 to 1 g based on 100 ml of the health beverage composition.
  • the dietary supplement further comprises a food supplement acceptable with the extracellular polysaccharide of the present invention, a mycelium culture medium of Seriphoria laccerata containing the same, a dry powder of the mycelium culture medium, or an extract of the mycelium culture medium. can do.
  • the present invention is an extracellular polysaccharide produced by Ceriporia lacerata ( Ceriporia lacerata ), mycelium culture medium of the seriporia laccerata comprising the extracellular polysaccharide, the dry powder of the mycelium culture medium, or the extract of the mycelium culture solution It provides a method for preventing or treating degenerative brain disease, comprising administering to a subject in need thereof.
  • the extracellular polysaccharide, mycelium culture medium of the three liporia laccerata containing the same, its dry powder or extract is as described above.
  • the subject of the method for preventing or treating degenerative brain disease may be a mammal, specifically a human.
  • the present invention is an extracellular polysaccharide produced by Ceriporia lacerata , for use in the manufacture of a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, Ceriporia comprising the extracellular polysaccharide A mycelium culture solution of lacserata, a dry powder of the mycelium culture solution, or an extract of the mycelium culture solution is provided.
  • the extracellular polysaccharide, mycelium culture medium of the three liporia laccerata containing the same, its dry powder or extract is as described above.
  • PDA potential dextrose agar
  • PDA culture strains 87 plastic cultures; after 2-3 passages in Difco, Becton Dickinson and Company, strains (hereinafter referred to as
  • the dry powder of the seriporia laccerata mycelium culture medium was prepared by pulverizing the lyophoric lactera mycelium culture medium prepared in Preparation Example 1 by vacuum freeze drying at 25 ° C. for 72 hours using a vacuum freeze dryer. .
  • the EPS prepared in Preparation Example 4 was dissolved in 0.1 M Na 2 SO 4 /0.05 M NaN 3 [adjusting pH to 4 with glacial acetic acid] to 1% (w / v), and then 4,000 rpm. After centrifugation for 0.5 hours, only the supernatant was filtered with a 0.45 ⁇ m syringe filter and analyzed by GPC.
  • the EPS molecular weight of the present invention was found to be about 120 kDa.
  • the EPS prepared in Preparation Example 4 was second purified and treated with proteolytic enzymes to determine sugar and protein content.
  • the first purified EPS (EPS prepared in Preparation Example 4) was dissolved in distilled water and centrifuged at 8,000 rpm for 20 minutes to separate the supernatant. Ethanol corresponding to 2-3 times the amount was added to the separated supernatant and placed in a 4 ° C. refrigerator for 12 hours. Thereafter, only the supernatant was taken from the stationary material, which was again centrifuged at 8,000 rpm for 20 minutes, and the precipitate was recovered to obtain a second purified EPS. After dissolving the second purified EPS in distilled water, the proteolytic enzyme alcalase was treated at 50 ° C. for 30 minutes at a concentration of 0.5% (w / v).
  • Sugar content was measured by the phenol-sulfuric acid method. Specifically, 25 ⁇ l of 80% (v / v) phenol was added to 1 mL of the diluted sample, 2.5 mL of sulfuric acid was added, cooled to room temperature, and absorbance was measured at 465 nm to calculate the sugar content.
  • protein content was measured by the BCA method (Smith PK et al., Analytical Biochemistry , 150 (1): 76-85, 1985) and bovine serum albumin was used as a standard.
  • the sugar content and protein content measured as described above are shown in Table 2 below, and the sugar content of EPS was 45 to 51 wt% and the protein content was 33 to 34 wt%.
  • Each value is mean ⁇ SE (n ⁇ 3).
  • EPS mainly contains mannose, galactose and glucose.
  • mice were assigned to eight Sprague-Dawley rats (7 weeks old, males, Samtako Co., Ltd.) weighing 205 ⁇ 5 g for each group, for a total of 40 animals.
  • the temperature of the feeding room was maintained at 22 ⁇ 3 °C and 50 ⁇ 20% of humidity, and the contrast was 12 hours. Water and diet were to be taken freely.
  • the experimental animals used were handled according to "Guide for the Care and Use of Laboratory Animals [Department of Health, Education, and Welfare Publication (National Institute of Health) 85-23, 1996]".
  • Groups II to V were inhaled anesthetized rats with isoflurane (2.5%) and then placed on medial septum (AP: -0.4, L: ⁇ 1.4, H: -3.5) using a stereotaxic apparatus.
  • a solution of 4 ⁇ g ⁇ -amyloid in 4 ⁇ l saline was added to a 10 ⁇ l gas-tight glass syringe (Hamilton, Reno, NV, USA) for a perfusion pump (Pump 22, Harvard). Apparatus, South Natick, MA, USA) was used for 5 minutes after 4 ⁇ l injection at 0.4 ⁇ l / min flow rate.
  • Group I was injected with artificial cerebrospinal fluid consisting of 145 mM NaCl, 2.7 mM KCl, 1.2 mM CaCl 2 , and 1.0 mM MgCl 2 in the same manner as described above.
  • group III 1 mg / kg of donepezil was orally administered once a day from ⁇ -amyloid to the end of the experiment.
  • Groups IV and V were orally administered EPS once a day from 4 weeks before ⁇ -amyloid administration to the end of the experiment at concentrations of 5.5 mg / kg and 16.5 mg / kg, respectively.
  • Rats prepared as in Reference Example 1 were used to measure the degenerative brain disease improvement effect of the EPS of the present invention through a Morris water maze experiment.
  • this experiment is to determine whether each test substance aids in the short and longterm memory recovery of rats.
  • Fill a circular bath 180 cm in diameter, 75 cm in height) with water 25 ⁇ 1 cm and hide the hide (24 cm in diameter) 1 cm below the water surface.
  • a space cue was installed on the slope of the wall to confirm the position, and the skim milk powder was dissolved in water so that the escape stand could not be visually checked.
  • Two days before and one day before the experiment all the experimental groups were allowed to swim freely in a circular tank without a shelter for 1 minute to adjust to the swimming situation.
  • animals were started in random order in two of the three areas except for the quadrant where the shelters were placed to find the shelters for 60 seconds.
  • the escape was found, it was allowed to stay on it for 20 seconds (position learning). If the escape was not found within 45 seconds, the experimenter guided the animal to the escape and allowed to stay for 20 seconds. As soon as 20 seconds of position learning was completed, the time and the moving distance from the animals to the evacuation zone were measured. If you go up to the escape, give 20 seconds to perform a total of four times a day. All data was taken with a camera mounted on a tank and analyzed with a video tracking system (Panlab, USA). At the end of the four-day experiment, a probe test was performed on the fifth day, 24 hours later, and a free swim was performed for 90 seconds without the escape pads.
  • Figure 1 is a long-term memory measurement results
  • Figure 2 is a short-term memory measurement results
  • Figure 3 is a final memory capacity evaluation results.
  • both the experimental group treated with a low concentration (5.5 mg / kg) and a high concentration (16.5 mg / kg) of the present invention showed a long-term memory improvement effect dependent on the EPS treatment concentration compared to the negative control.
  • the final memory capacity evaluation result showed that the experimental groups IV and V showed an improvement in memory capacity depending on the EPS treatment concentration compared to the negative control.
  • the experimental group V showed a significant improvement in balance sensation compared to the negative control (p ⁇ 0.05).
  • the effect of improving balance sensation was shown depending on the EPS treatment concentration.
  • the EPS of the present invention has an effect of improving the motor coordination and the sense of balance that is degraded due to brain damage caused by degenerative brain disease.
  • the experimental animals were dissected to measure the content of acetylcholine in the brain tissues to determine the treatment effect of the degenerative brain disease.
  • the rats were dislocated and sacrificed after sacrificing the experiments of Examples 2 to 4, and the brains were aseptically extracted and washed twice with HBSS (Hank's balanced salt solution, Gibco, Grand Island, NY, USA). 50 ⁇ l of 1% hydroxylamine (Sigma, USA) was added to 50 ⁇ l of washed brain tissue, and then pH was adjusted to 1.2 ⁇ 0.2 using hydrochloric acid. After adding 500 ⁇ l of FeCl 3 and measuring the absorbance at 530 nm, the content of acetylcholine ( ⁇ mol / mg protein) was measured. The results are shown in FIG. 6.
  • the experimental animals were dissected to determine the content of acetylcholine esterase in the brain tissues to determine the treatment effect of the degenerative brain disease.
  • the brain tissue of the rat was isolated in the same manner as in Example 5, followed by 300 ⁇ l of 0.1 M Tris buffer (pH 8.0) and 20 ⁇ l of 0.01 M dithionitrobenzoic acid (DTNB; Sigma, USA). 10 ⁇ l of 0.1 M acetylthiocholine chloride (Sigma, USA), a substrate, was added to 10 ⁇ l of brain tissues of the brain tissue, and the absorbance change of acetylcholine esterase (unit / min / mg protein) was measured at 405 nm. Measurement was made for 5 minutes and the results are shown in FIG. 7.
  • experimental group IV showed 14.39% improved acetylcholine esterase activity inhibition effect compared to the negative control group
  • experimental group V showed 19.48% improved acetylcholine esterase activity inhibitory effect compared to the negative control group.

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Abstract

La présente invention concerne une composition pharmaceutique qui permet de prévenir ou de traiter des maladies dégénératives du cerveau et qui comprend, en tant que principe actif, un polysaccharide extracellulaire produit par Ceriporia lacerata, un liquide de culture de mycélium de Ceriporia lacerata, contenant le polysaccharide extracellulaire, une poudre sèche du liquide de culture de mycélium ou un extrait du liquide de culture de mycélium, la composition pouvant être utile pour prévenir ou traiter divers types de maladies dégénératives du cerveau.
PCT/KR2017/001651 2016-02-16 2017-02-15 Composition pharmaceutique pour prévenir ou traiter les maladies dégénératives du cerveau, contenant un polysaccharide extracellulaire produit par ceriporia lacerata en tant que principe actif WO2017142306A1 (fr)

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KR101691975B1 (ko) * 2016-02-16 2017-01-02 (주)퓨젠바이오농업회사법인 세리포리아 락세라타에 의해 생산되는 세포외다당체를 유효성분으로 함유하는 퇴행성 뇌질환 예방 또는 치료용 약학 조성물

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KR20160008431A (ko) * 2014-07-14 2016-01-22 (주)퓨젠바이오농업회사법인 세리포리아 락세라타 배양액 추출물 유래의 세포외다당체를 유효성분으로 함유하는 지질 관련 대사 개선용 조성물
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