WO2009091130A2 - Composition for prevention and treatment of the dementia - Google Patents

Composition for prevention and treatment of the dementia Download PDF

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Publication number
WO2009091130A2
WO2009091130A2 PCT/KR2008/007751 KR2008007751W WO2009091130A2 WO 2009091130 A2 WO2009091130 A2 WO 2009091130A2 KR 2008007751 W KR2008007751 W KR 2008007751W WO 2009091130 A2 WO2009091130 A2 WO 2009091130A2
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WO
WIPO (PCT)
Prior art keywords
herbal mixture
extract
fructus
dementia
hot
Prior art date
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PCT/KR2008/007751
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English (en)
French (fr)
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WO2009091130A3 (en
Inventor
Hyun Su Bae
Moon Kyu Kang
Jae Yoon Kim
Na Youn Lee
Young Eun Kim
In Sop Shim
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Purimed Co., Ltd.
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Application filed by Purimed Co., Ltd. filed Critical Purimed Co., Ltd.
Publication of WO2009091130A2 publication Critical patent/WO2009091130A2/en
Publication of WO2009091130A3 publication Critical patent/WO2009091130A3/en

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Classifications

    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/884—Alismataceae (Water-plantain family)
    • 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)
    • A61K36/40—Cornaceae (Dogwood family)
    • 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)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A61K36/804—Rehmannia
    • 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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/894—Dioscoreaceae (Yam family)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/894—Dioscoreaceae (Yam family)
    • A61K36/8945—Dioscorea, e.g. yam, Chinese yam or water yam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention relates, in general, to a composition for prevention and treatment of neurodegenerative diseases associated with learning ability, powers of memory and cognitive ability and, more particularly, to a composition for the prevention and treatment of dementia comprising a hot-water soluble extract of a herbal mixture (so-called ⁇ Koo Gi Ji Hwang Tang' ) including Steamed Rehmannia Radix, Lycium Fructus, Discoreae Rhizoma, Cornus Fructus, Hoelen, Moutan Cortex Radicis and Alismatis Rhizoma.
  • Oriental herbs contain lots of useful substances, which have been used to treat a variety of neurodegenerative diseases, and it has been reported that oriental herbs function to suppress the expression of neurodegenerative diseases .
  • the present inventors have made continuous attempts to treat dementia using herbal medicine, and found that, from the fact that an extract, which is obtained by- extracting herbs selected from the group consisting of Steamed Rehmannia Radix, Lycium Fructus, Discoreae Rhizoma, Cornus Fructus, Hoelen, Moutan Cortex Radicis and Alismatis Rhizoma with alcohol or an aqueous alcohol solution, is effective in improving the memoryretention, the herbal alcohol extract may be used to prevent and treat dementia or Alzheimer' s disease since memory loss is one of the characteristics of patients suffering from dementia or Alzheimer's disease (Korean Patent No. 491429).
  • an object of the present invention is to provide a pharmaceutical composition capable of preventing and treating dementia or Alzheimer' s disease by suppressing the loss of learning and cognitive abilities, the failure of memory, and the loss of activity of choline acetyltransferase.
  • Another object of the present invention is to provide a health supplement food capable of preventing and treating dementia or Alzheimer's disease.
  • the present invention provides a pharmaceutical composition for prevention and treatment of dementia comprising a hot-water soluble extract of an herbal mixture as an effective component, wherein the herbal mixture includes Steamed Rehmannia Radix, Lycium Fructus, Discoreae Rhizoma, Cornus Fructus, Hoelen, Moutan Cortex Radicis, and Alismatis Rhizoma in a weight ratio (w/w) of 30 to 40 : 30 to 40 : 10 to 20 : 10 to 20 : 5 to 10 : 5 to 10 : 5 to 10.
  • the present invention provides a health supplement for prevention and treatment of dementia comprising a hot-water soluble extract of an herbal mixture and a sitologically acceptable food supplement, wherein the herbal mixture includes Steamed Rehmannia Radix, Lycium Fructus, Discoreae Rhizoma, Cornus Fructus, Hoelen, Moutan Cortex Radicis, and Alismatis Rhizoma in a weight ratio (w/w) of 30 to 40 : 30 to 40 : 10 to 20 : 10 to 20 : 5 to 10 : 5 to 10 : 5 to 10.
  • the composition according to one exemplary embodiment of the present invention may be useful to be taken as medicine for an extended time period for the purpose of the prevention of dementia since the composition includes as an effective component the herbal medicine extract which has neither toxicity nor side effects.
  • the composition according to one exemplary embodiment of the present invention does not cause toxic side effects even when people take it as medicine for an extended time period or take excessive amounts of the medicine since the composition comprises herbal components in an effective amount and is formulated into a final product that may be easily used by the general public. Therefore, the composition may be useful in preventing and continuously treating dementia by allowing anyone to take the medicine as a therapeutic composition or health foods.
  • composition according to one exemplary embodiment of the present invention may be usefully used as a functional food or health food for researchers and the general public since the composition improves learning ability, cognitive ability, memory retention, etc.
  • FIG. 1 is a graph illustrating the comparison of cognitive abilities of four groups of rats in a Morris water maze experiment.
  • each maze experiment on each group is conducted 4 times a day for 6 days to calculate an average of moving/swimming time (Efficiency under comparison with corresponding data of normal groups : *p ⁇ 0.05; Efficiency under comparison with corresponding data of a TMT-treated group: #p ⁇ 0.05; and Efficiency under comparison with corresponding data of a TMT-treated group: ##p ⁇ 0.01).
  • FIG. 2 is a graph illustrating the comparison of cognitive abilities of four groups of rats in a Morris water maze experiment. Here, an average of platform/swimming time per experiment is represented as a percentage (Efficiency under comparison with corresponding data of a TMT-treated group: ###p ⁇ 0.001).
  • FIG. 3 is a photograph illustrating the distribution of ChAT immunoreactive cells in Hippocampus regions, CAl and CA3, of the normal TMT, TMT+LF and TMT+GJT groups after surgery has been performed on the rats on the seventh day of the Morris water maze experiment.
  • FIG. 4 is a photograph illustrating the distribution of PKC immunoreactive cells in Hippocampus regions, CAl and CA3, of the normal TMT, TMT+LF and TMT+GJT groups after surgery has been performed on the rats on the seventh day of the Morris water maze experiment.
  • composition according to one exemplary embodiment of the present invention includes, as an effective component, a hot-water soluble extract of an herbal mixture
  • LiBoscHiTz has pharmacological effects including a hypoglycemic effect, cardiotonic and diuretic effects on the circulatory system, a hepatoprotective effect and an antibacterial effect, etc.
  • Lycium Fructus ⁇ Lycium chinense M ILL .) has a non-specific immune stimulant effect.
  • Lycium Fructus significantly enhances the phagocytosis of the reticuloendothelial system, and a regulatory effect.
  • a soup obtained by boiling Lycium Fructus has a hematopoietic effect and acts as a biostimulant to highly increase the number of eggs when chickens are fed with the biostimulant.
  • it has pharmacological effects such as hypotensive and hypoglycemic effects, reduction in serum cholesterol level, an anti-fatty liver effect, a growth- stimulating effect, cancer cell proliferation inhibitive activity and an increase in the weight of the uterus, etc.
  • Discoreae Rhizoma (Discorea batatas D ECNE -) has pharmacological effects such as a hypoglycemic effect, excellent harmonic effects in the intestinal tract of the digestive system, and extends the lifespan because of its antioxidative effects, etc.
  • Cornus Fructus (Cornus officinalis Si EB . et Zuco) has pharmacological effects such as a hypoglycemic effect, a diuretic effect, an antihypertensive effect, an effect on the suppressions of Staphylococcus sp. and Shigella sp., inhibitive activity on the proliferation of ascites cancer, a lymphoproliferative effect on the immune system, an effect on the inhibition of platelet aggregation, an effect on an increase in contractile force of heart muscle, etc.
  • Hoelen Poria cocos (F R . ) W OLF ) has pharmacological effects such as a diuretic effect, a hypoglycemic effect, an effect on an increase in contractile force of the heart muscle, an immune stimulant effect, etc.
  • Moutan Cortex Radicis (Paeonia suffruticosa A NDR ) has pharmacological effects such as alleviation of pain, relief, removal of fever, an anticonvulsive effect, an antiinflammatory effect, an antithrombogenic effect, an antiallergic effect, an effect on the suppression of gastric juice secretion, etc.
  • Alismatis Rhizoma ⁇ Alisma canaliculatum A. B R . et B OUCHE ) has pharmacological effects such as a diuretic effect, an effect on the improvement of tinnitus and worsening eye sight, etc.
  • the composition for prevention and treatment of dementia includes a hot-water soluble extract as an effective component, wherein the hot-water soluble extract is prepared by mixing Steamed Rehmannia Radix, Lycium Fructus, Discoreae Rhizoma, Cornus Fructus, Hoelen, Moutan Cortex Radicis and Alismatis Rhizoma, each of which has the above-mentioned pharmacological effects, in a weight ratio (w/w) of 30 to 40 : 30 to 40 : 10 to 20 : 10 to 20 : 5 to 10 : 5 to 10 : 5 to 10 and extracting the herbal mixture with hot water.
  • w/w weight ratio
  • a hot-water soluble extract is prepared by adding impurity-free distilled water, particularly deionized water, to the herbal mixture and extracting the herbal mixture at 80 to 100 0 C for 1 to 3 hours.
  • impurity-free distilled water particularly deionized water
  • the hot-water extraction is conducted at a temperature below 80 0 C for a time period shorter than 1 hour, the effective components are not easily eluted from the herbal mixture, whereas when the hot-water extraction is conducted at a temperature above 100 0 C for a time period longer than 3 hours, the effective components may be discomposed. Therefore, it is preferred to conduct the hot-water extraction within the given ranges of temperature and time. Meanwhile, the hot-water extraction may be conducted using reflux extraction or vacuum distillation, and the reflux extraction is preferred.
  • the herbal medicine extract according to one exemplary embodiment of the present invention may be used in the field of various applications by extracting the herbal mixture with hot water, followed by filtering and concentrating the extract, or freeze-drying the concentrated extract.
  • the present invention provides a pharmaceutical composition including, as an effective component, the herbal medicine extract prepared according to the method, wherein the composition is effective in preventing and treating diseases such as dementia.
  • the composition according to one exemplary embodiment of the present invention preferably includes 0.01 to 99.9% by weight, and more preferably 0.1 to 50% by weight of the herbal medicine extract.
  • the content of the herbal medicine extract may be varied according to the condition of the patient, the severity of disease, and the kind and progress of disease, but the present invention is not particularly limited thereto.
  • the composition comprising the herbal medicine extract according to one exemplary embodiment of the present invention may further include a suitable carrier, vehicle and diluent, all of which are widely used in the preparation of pharmaceutical compositions.
  • composition according to one exemplary embodiment of the present invention may be formulated into oral formulations such as powders, granules, tablets, capsules, a suspension, an emulsion, a syrup and an aerosol, and external preparations, and also may be formulated in the form of a suppository and sterile injection.
  • the carrier, vehicle and diluent that may be included in the composition comprising the herbal medicine extract includes, but is not particularly limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oils.
  • the diluent or vehicle such as a filler, an extender, a binder, a wetting agent, a disintegrant and a surfactant is generally used.
  • a solid formulation for oral delivery includes a tablet, a pill, powders, granules, a capsule, and the like, and the solid formulation is prepared by mixing at least one vehicle, for example starch, calcium carbonate, sucrose or lactose and gelatin, with the hot-water soluble extract.
  • lubricants such as magnesium, styrate and talc are also used herein.
  • a liquid formulation for oral delivery includes a suspension, a solution, an emulsion, a syrup, etc.
  • a variety of vehicles for example a wetting agent, a sweetener, an aromatic, a preservative and the like may be included in the liquid formulation.
  • a formulation for parenteral delivery includes a sterile aqueous solution, an insoluble solvent, a suspension, an emulsion, a freeze dryer, a suppository, etc.
  • Vegetable oils such as propylene glycol, polyethylene glycol and olive oil, and injectable ester such as ethyl oleate may be used as the insoluble solvent and the suspension, respectively.
  • Basic materials of the suppository that may be used herein comprise witepsol, macrogol, Tween 61, cacao butter, sevum laurinum, glycerogelatin, etc.
  • a composition may, for example, be administered in a dose equal to or 2, 3 or 4 times higher than the single dosage, or be administered in a dose 1/2, 1/3 or 1/4 times lower than the single dosage.
  • the single dosage refers to a dose in which an effective drug is administered once.
  • the single dosage corresponds to the equivalent dose, or a dose 1/2, 1/3 or 1/4 times lower than the daily dosage.
  • the desirable dose of the composition of the present invention may be suitably varied according to the condition and body weight of a patient, the severity of disease, the dosage form, the route and time of administration, but may be easily selected by those skilled in the art.
  • the extract of the present invention is administered daily in a dose of 100 to 800 mg/kg, and preferably 100 to 600mg/kg.
  • the administration may be conducted once or twice a day, or may be conducted several times, and preferably 1 to 6 times.
  • the herbal medicine extract of the present invention is orally and intraperitoneally administered, and subcutaneously injected to white rats to conduct a toxicity test.
  • the herbal medicine extract is intraperitoneally administered in a dose of at least 5 g/kg, the herbal medicine extract is proven to be safe at the minimum lethal dose (MLD) in the toxicity test.
  • MLD lethal dose
  • the present invention provides a health supplement for the treatment of dementia comprising the herbal medicine extract as an effective component.
  • the hot-water soluble extract of the present invention may be used in the food, alone or in combinations with other food or food components.
  • the hot-water soluble extract may be suitably used according to the conventional methods.
  • the extract of the present invention may be added in a content of 0.01 to 1 % by weight, and preferably 0.2 to 0.6 % by weight, based on the total weight of the extract materials.
  • the extract of the present invention may be used in an effective dose, based on the effective dose of the pharmaceutical composition, but may be used in a dose lower than the dose range when patients are fed for an extended time period for the purpose of health and hygiene or for the purpose of health management.
  • the effective components may be used in a dose greater than the dose range since it is safe and is without any side effects.
  • the kinds of the food There is no particular limitation on the kinds of the food.
  • the food to which the effective components may be added include, but are not particularly limited to, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, instant noodles, other noodles, gum, dairy products including ice cream, various soups, beverages, teas, drinks, alcoholic drinks and vitamin cocktails.
  • the foods include folk remedies such as an antianaemic agent, medicine to aid virility, a skin whitening agent and the like for the purpose of the above effects.
  • a variety of oriental medical remedies such as Choung Sim Gang Hwa Tang may also be used herein.
  • ⁇ 1-1> Preparation for animal test Male Sprague-Dawley rats weighing 250 to 28Og were used. These laboratory animals were purchased from SAMTAKO INC. (kyunggi-do, Korea) . Before the experiment, the laboratory animals were adapted to a laboratory environment for at least one week. The laboratory animals were raised in private cages under light-controlled conditions (12/12- hr light/dark cycles) . The temperature in a breeding room was maintained to 23 0 C, and the laboratory animals were fed with animal feed and water without restrictions .
  • the laboratory animals were divided into four groups, and each group was treated with drugs.
  • Normal group - a group that is not treated in any ⁇ way with a drug.
  • this group is referred to as "Normal” or "Nor.”
  • TMT Trimethyltin
  • TMT/herbal mixture extract-treated group - a group in which 6.0 mg/kg of TMT is dissolved in 0.9% saline and intraperitoneally administered to laboratory animals, the laboratory animals return to their own cages, and 400 mg/kg of the herbal mixture extract is dissolved in saline and orally administered to the laboratory animals for 2 weeks.
  • this group is referred to as "TMT+GJT.”
  • TMT/Lycium Fructus-treated group - a group that is treated in the same manner as in the TMT+GJT group, except that Lycium Fructus is used instead of the herbal mixture extract.
  • this group is referred to as "TMT+LF .
  • a Morris water maze is a round water bath made of fiberglass-stacked material.
  • the Morris water maze is painted white, and has a diameter of 200 cm and a height of 35 cm.
  • the water maze was filled with water up to a height of 21 cm, and the water temperature was maintained to 23 ⁇ 2 Q C.
  • the water bath was divided into four quadrant regions in all directions at the same distance from the girth of the water bath.
  • a transparent escape platform with a diameter of 15 cm and a height of 20 cm was located apart at a distance of approximately 50 cm from a wall of the water bath, and positioned at a distance of 1.5 cm below the water level in the center of the northeast quadrant region.
  • the TMT-treated group has a very significant difference in time, compared to the normal group. This indicates that TMT damages memory power of the rats by destroying their cholinergic neurons.
  • the TMT/herbal medicine extract-treated group had no significant time difference with respect to the normal group, but had a significant time difference with respect to the TMT-treated group for the time period from the 1 st to the 5 th day.
  • the TMT/herbal medicine extract-treated group showed no significant difference in the total percentage of the time that the laboratory animals stayed in the quadrant region including the escape platform, as measured on the day when the escape platform was removed on the 7 th day of the administration and the water maze test was carried out. Also, it was revealed that the TMT/herbal medicine extract-treated group showed significant difference in the total percentage of time in respect to the TMT-treated group. From the experimental results, it was revealed that the memory retention of the rats was recouped since the cholinergic neurons damaged by TMT were recovered by the administration of the composition of the present invention.
  • a Hippocampus region of each rat was subject to choline acetyltransferase (ChAT) and protein kinase (PKC) immunohistochemical staining to observe cholinergic neurons and down-stream signal transduction-associated proteins.
  • ChAT choline acetyltransferase
  • PKC protein kinase
  • the laboratory animals were anesthetized with sodium pentobarbital (100mg/kg, i.p.) right after all the behavior tests were completed, and a 4% formalin fixative was perfused through the hearts of the rats, their brains were taken out, and fixed with the same fixative for 2 to 3 hours.
  • Each extracted brain tissue was cut to a thickness of 30 ⁇ m along an inner middle region of dorsal and ventral Hippocampus by using a microtome (Leica, CM1850, Germany) , and cultured with primary sheep polyclonal ChAT antibody and PKC antibody (Cambridge Research Biochemicals, Wilmington, DE, USA) at 4°C for 72 hours while being stirred continuously.
  • the brain tissue was washed three times with PBST, and reacted at room temperature for 2 hours with biotinylated anti-sheep serum (Vector Laboratories, Burlingame, CA, USA), which was diluted 200 times, in PBST supplemented with 2% rabbit serum. Then, the brain tissue was dipped in a Vectastain Elite ABC reagent (Vector) at room temperature for 2 hours, washed several times with PBS, strengthened with nickel chloride, and then developed using diaminobenzadine (DAB) as a coloring agent.
  • Vector Vectastain Elite ABC reagent
  • the composition according to one exemplary embodiment of the present invention may be used to prevent and treat dementia since it recovers the impaired learning ability, memory power and cognitive ability of dementia patients.
  • a food or beverage composition comprising as an effective component the herbal mixture prepared in Example 1 was prepared, as follows.
  • Example 1 522 mg of honey, 5 mg of thioctic acid amide, 10 mg of nicotinamide, 3 mg of riboflavin sodium hydrochloride, 2 mg of pyridoxine hydrochloride, 30 mg of inositol, 50 mg of orotic acid and 200 ml of water were homogeneously mixed, and the resulting mixture was formulated into a beverage by using one of the conventional methods.

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PCT/KR2008/007751 2007-12-28 2008-12-29 Composition for prevention and treatment of the dementia WO2009091130A2 (en)

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KR10-2007-0139575 2007-12-28
KR1020070139575A KR20090071704A (ko) 2007-12-28 2007-12-28 치매 예방 및 치료용 조성물

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Cited By (2)

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EP3235502A4 (en) * 2014-12-19 2018-07-18 Dong-A ST Co., Ltd. Composition containing poria cocos bark extract for preventing, improving or treating neurodegenerative disorders
US10588927B2 (en) 2014-12-19 2020-03-17 Neurobo Pharmaceuticals, Inc. Composition containing mixed extract of mulberry and Poria cocos peel

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CN105106760A (zh) * 2015-09-30 2015-12-02 山东大学齐鲁医院 一种治疗小儿脑瘫的中药及其制备方法
KR20180115823A (ko) * 2017-03-31 2018-10-24 강기원 치매 예방 및 개선용 식품 조성물
KR102092509B1 (ko) * 2019-09-02 2020-03-23 강기원 치매 예방 및 개선용 식품 조성물

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EP3235502A4 (en) * 2014-12-19 2018-07-18 Dong-A ST Co., Ltd. Composition containing poria cocos bark extract for preventing, improving or treating neurodegenerative disorders
US10588927B2 (en) 2014-12-19 2020-03-17 Neurobo Pharmaceuticals, Inc. Composition containing mixed extract of mulberry and Poria cocos peel
EP3632454A1 (en) * 2014-12-19 2020-04-08 NeuroBo Pharmaceuticals, Inc. Composition containing poria cocos bark extract for preventing, improving or treating neurodegenerative disorders
US10864238B2 (en) 2014-12-19 2020-12-15 Neurobo Pharmaceuticals, Inc. Composition containing Poria cocos peel extract for treating neurodegenerative disorders
US10946053B2 (en) 2014-12-19 2021-03-16 Neurobo Pharmaceuticals, Inc. Composition containing mixed extract of mulberry and Poria cocos bark for preventing, improving or treating neurodegenerative disorders
CN113712998A (zh) * 2014-12-19 2021-11-30 纽罗博制药有限公司 预防、改善或治疗退行性神经系统疾病的含茯苓皮提取物的组合物

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