WO2024117389A1 - Composition pharmaceutique pour la prévention ou le traitement de la démence sénile, et son procédé de préparation - Google Patents

Composition pharmaceutique pour la prévention ou le traitement de la démence sénile, et son procédé de préparation Download PDF

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WO2024117389A1
WO2024117389A1 PCT/KR2023/003269 KR2023003269W WO2024117389A1 WO 2024117389 A1 WO2024117389 A1 WO 2024117389A1 KR 2023003269 W KR2023003269 W KR 2023003269W WO 2024117389 A1 WO2024117389 A1 WO 2024117389A1
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dementia
preventing
vinegar
weight
licorice
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PCT/KR2023/003269
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Korean (ko)
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권혁분
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권혁분
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  • the present invention relates to a composition for preventing or improving dementia and a method for producing the same.
  • Alzheimer's disease is the most important disease among senile dementias, and the accumulation of beta-amyloid in the brain and the resulting neurotoxicity are known to be important causes (ProbstA et al, Brain Pathol, 1:229-239, 1991).
  • beta-amyloid is known to create plaques in which proteins accumulate and tangle in the brain, which causes Alzheimer's disease (Breimer LH, et alNature, 326: 749-750, 1987).
  • beta-amyloid is made from amyloid precursor protein (APP) through the sequential action of beta-secretase (BACE1) and gamma-secretase, which are membrane protein hydrolases.
  • BACE1 beta-secretase
  • gamma-secretase membrane protein hydrolases.
  • This beta-amyloid can be broadly divided into two types: A ⁇ 40 and A ⁇ 42, which consist of 40 or 42 amino acids.
  • a ⁇ 40 accounts for the majority, but A ⁇ 42, which is produced in relatively small quantities, is pointed out as the most important pathogen because it easily creates plaques (Selkoe, Science 298: 789-891, 2002).
  • tacrine Cognex, 1994
  • donepezil Aricept, 1996)
  • the mechanism of action of the above drugs is to prevent dementia by increasing the concentration of acetylcholine, a neurotransmitter, by inhibiting the activity of the enzyme acetylcholinesterase (AChE), an enzyme that decomposes acetylcholine, which plays a central role in the central nervous system. and is known to treat.
  • AChE acetylcholinesterase
  • tacrine is expensive compared to its efficacy and has the problem of serious hepatotoxicity
  • donecortex has no hepatotoxicity, but stimulates the parasympathetic nerves and is known to have various side effects such as vomiting, nausea, and diarrhea.
  • the purpose of the present invention is to provide a pharmaceutical composition for preventing or ameliorating dementia, comprising as an active ingredient a heated mixture of Beopje Manchuria, licorice, rhubarb, swim bladder, and vinegar.
  • Another object of the present invention is to provide a health functional food for the prevention or improvement of dementia containing as an active ingredient a heated mixture of Beopje Mancho, licorice, rhubarb, swim bladder and vinegar.
  • Another object of the present invention is to provide a method for producing a composition for preventing or improving dementia containing as an active ingredient a heated mixture of Beopje Mancho, licorice, rhubarb, swim bladder, and vinegar.
  • composition for preventing or ameliorating dementia of the present invention for achieving the above object is characterized by containing as an active ingredient a heated mixture of Beopje mango, licorice, rhubarb, swim bladder, and vinegar.
  • the mixing ratio of the above-mentioned seaweed, licorice, rhubarb, swim bladder and vinegar is 20 to 50 parts by weight, 10 to 50 parts by weight of licorice, 10 to 50 parts by weight of rhubarb, and 50 to 100 parts by weight of vinegar, based on 100 parts by weight of the swim bladder. It is characterized by denial.
  • the dementia is characterized as one or more diseases selected from the group consisting of Alzheimer's dementia, cerebrovascular dementia, and dementia caused by senile dementia.
  • the method for producing a composition for preventing or improving dementia of the present invention includes the steps of adding water to licorice, rhubarb and swim bladder and heating them, adding vinegar to the heated water and heating it, and the vinegar It is characterized in that it includes the step of adding and heating the added heating material.
  • composition for preventing or improving dementia according to the present invention is stable as it does not cause toxicity to cells, and can inhibit the production of beta-amyloid, a known causative agent of dementia, especially Alzheimer's disease, thereby preventing dementia.
  • beta-amyloid a known causative agent of dementia, especially Alzheimer's disease, thereby preventing dementia.
  • it has the advantage of being able to be effectively used in treatment.
  • Test Example 1 is a graph showing the results of Test Example 1 according to the present invention.
  • Figure 2 is a graph showing the results of Test Example 2 according to the present invention.
  • Figures 3 and 4 are graphs showing the results of Test Example 3 according to the present invention.
  • dementia in general, refers to a disease in which a normal intellectual level is maintained during the growth period, but cognitive function impairment and personality changes occur later. Dementia is caused by the destruction of cranial nerves due to various causes, resulting in overall mental dysfunction such as memory impairment, language impairment, fecal incontinence, paranoid thinking, and aphasia. In the process, psychiatric symptoms such as depression, personality disorder, and aggression appear. It is also accompanied by The medical community is paying attention to the causal factors caused by aging and genetics, but the exact cause and treatment have not yet been identified. Diseases classified as dementia are not limited to this, but may include any one of Alzheimer's dementia, cerebrovascular dementia, and senile dementia, and the composition provided by the present invention is a disease that can be treated, prevented, and improved. It can be included.
  • composition for preventing or improving dementia contains as an active ingredient a heated mixture of Beopje mango, licorice, rhubarb, swim bladder, and vinegar, and beta-amyloid, which is known to be a cause of dementia due to the interaction of each ingredient. By suppressing its production, it prevents or improves dementia, is good for the kidneys, and clears the mind.
  • the Beopje Mango is a refined product of the sulfate mineral Mango, and mainly contains sodium sulfate.
  • bakcho the first crystals that precipitate
  • beopje mangcho the crystals obtained by repeated recrystallization
  • Beopje Mangcho has been used for many symptoms of constipation.
  • the Beopje Mangcho also has an analgesic effect.
  • the legume decoction can be purchased and used commercially.
  • the licorice (Glycyrrhiza uralensis) is a perennial herb belonging to the legume family and is grown or grown in northern China, Siberia, southern Italy, Manchuria, and Mongolia. Licorice is used as an ingredient to reduce toxicity in all herbal medicine prescriptions and is one of the herbs used as an antitussive (Rauchensteiner F. et al., JPharmBiomedAnal., 38(4), pp.594-600, 2005), and in Europe, it is used in tobacco, gum, and It is also used to sweeten candies. Recent research results show that licorice alleviates oxidative damage to the kidneys (Yokozawa T.
  • licorice can be purchased and used commercially, or collected or cultivated directly from nature, and is not limited thereto. Additionally, there is no limitation as to whether or not it is dried.
  • the rhubarb (Rhei Rhizoma) is the root and rhizome of Janggun, a perennial herb belonging to the Rhizoma family, and its close relatives. There are about 15 species of plants, including Rheum coreanum Nakail and Pheum undulatumLinne in Korea. In China, the dried roots and rhizomes of Rheum palmatum Linne, Pheum tanguticum Maxim, and medicinal rhubarb (Rheum offcinale Baill) are its origin. there is.
  • Rhubarb is also clinically applied to the treatment of indigestion, constipation, acute inflammation, infectious diseases, parasitic diseases, bleeding, thrombocytopenia, burns, and skin diseases. It is also very effective in treating boils and phlegm.
  • the rhubarb can be purchased and used commercially, or collected or cultivated directly from nature, and is not limited thereto. Additionally, there is no limitation as to whether or not it is dried.
  • the swim bladder refers to an air sac in a fish, and is used as a raw material for isinlass, a high-quality glue. In the present invention, it is most preferable to use a croaker swim bladder as the swim bladder, but this is not necessarily limited.
  • the vinegar is a fermented food that has been used since ancient times regardless of the East or West. It contains over 60 types of organic acids and is effective in relieving fatigue, preventing adult diseases, and increasing appetite.
  • the type of vinegar is not limited, and any commercially available vinegar can be purchased and used.
  • the mixing ratio of the legal mantra, licorice, rhubarb, swim bladder and vinegar is 20 to 50 parts by weight of legal mantra, 10 to 50 parts by weight of licorice, 10 to 50 parts by weight of rhubarb, and 50 to 50 parts by weight of vinegar, based on 100 parts by weight of the swim bladder. It is preferable that it is 100 parts by weight, because this ratio can show the best effect in preventing or improving dementia.
  • composition of the present invention may be a pharmaceutical composition, and the composition may contain the above-described mixed powder alone, or may include one or more pharmaceutically acceptable carriers, excipients, or diluents.
  • the pharmaceutically effective amount of the mixed powder is 0.5 to 100 mg/day/kg of body weight, preferably 0.5 to 5 mg/day/kg of body weight.
  • the pharmaceutically effective amount may vary appropriately depending on the degree of dementia symptoms, the patient's age, weight, health status, gender, administration route, and treatment period.
  • pharmaceutically acceptable as used herein refers to a composition that is physiologically acceptable and does not usually cause gastrointestinal disorders, allergic reactions such as dizziness, or similar reactions when administered to humans.
  • the carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Examples include polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers and preservatives may be additionally included.
  • compositions of the present invention can be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal.
  • the dosage form may be in any of the following forms: powder, granule, tablet, pill, emulsion, syrup, or soft or hard gelatin capsule.
  • composition according to the present invention is preferably administered orally, and the dosage of the active ingredient may be appropriately selected depending on various factors such as the route of administration, the patient's age, gender, weight, and patient's severity.
  • composition for preventing or improving dementia of the present invention can be added to food for the purpose of preventing or improving dementia symptoms, so the composition of the present invention can be used as a food composition for preventing or improving dementia symptoms.
  • the food composition for preventing and improving dementia of the present invention can be easily used as a food effective in preventing or improving dementia symptoms, such as a main ingredient, secondary ingredient, food additive, functional food or beverage.
  • Foods to which the composition for preventing and improving dementia symptoms according to the present invention can be added include, for example, various foods, beverages, gum, tea, vitamin complexes, functional foods, etc. Additionally, foods in the present invention include special nutritional foods (e.g., infant formula, infant and toddler food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g., ramen, noodles, etc.), breads, health supplements, and seasonings. Food (e.g. soy sauce, soybean paste, red pepper paste, mixed paste, etc.), sauces, confectionery (e.g. snacks), candy, chocolate, gum, ice cream, dairy products (e.g.
  • special nutritional foods e.g., infant formula, infant and toddler food, etc.
  • processed meat products e.g., fish products, tofu, jelly, noodles (e.g., ramen, noodles, etc.), breads, health supplements, and seasonings.
  • Food e.g. soy sauce, soybean paste, red pepper paste, mixed paste
  • fermented milk, cheese, etc. other processed foods, kimchi, It includes, but is not limited to, pickled foods (various kimchi, pickled vegetables, etc.), beverages (e.g., fruit drinks, vegetable drinks, soy milk, fermented drinks, etc.), and natural seasonings (e.g., ramen soup, etc.).
  • pickled foods various kimchi, pickled vegetables, etc.
  • beverages e.g., fruit drinks, vegetable drinks, soy milk, fermented drinks, etc.
  • natural seasonings e.g., ramen soup, etc.
  • the food, beverage or food additive can be manufactured by conventional manufacturing methods.
  • the above-mentioned functional food refers to a food group or food composition in which added value is added to the food to function and express the function of the food for a specific purpose using physical, biochemical, biotechnological methods, etc., and the regulation of biological defense rhythm, disease prevention and recovery. It refers to food that has been designed and processed to fully express the body's regulatory functions related to the body, etc., and may specifically be a health functional food.
  • the functional food may include food auxiliary additives that are foodologically acceptable, and may further include appropriate carriers, excipients, and diluents commonly used in the production of functional foods.
  • the amount of the composition according to the present invention may be 0.001% by weight to 100% by weight of the total weight of the food.
  • the method for producing the composition according to the present invention includes the steps of adding water to licorice, rhubarb, and swim bladder and heating them, adding vinegar to the heated product and heating it, and adding a legal agent to the heated product to which the vinegar has been added. It is characterized in that it includes the step of adding peppermint and heating it.
  • vinegar is added to the heated product and heated again at 80-100°C for 10-20 minutes.
  • composition prepared as described above can be taken as is, or can be formulated and taken. At this time, additional formulation methods are not limited.
  • the solid matter in the heated product to which the legal mango is added is pulverized to about 100 to 300 msh, and then dried. At this time, the drying method is not limited.
  • the reason for drying after pulverizing in the present invention is to consider the material characteristics of bladders, etc., and because it is difficult to powder when pulverizing after drying.
  • composition prepared as described above is in powder form and can be taken as is, or can be formulated into pills, liquids, etc., and the method of further formulation is not limited.
  • the amount of each material used is preferably 20 to 50 parts by weight of Beopje Mancho, 10 to 50 parts by weight of licorice, 10 to 50 parts by weight of rhubarb, and 50 to 100 parts by weight of vinegar, based on 100 parts by weight of swim bladder. This is to increase prevention and improvement effects.
  • composition of the present invention has the advantage of being effective in treating or preventing not only dementia but also epilepsy.
  • the above-described heated product was pulverized so that the solid content in the heated product was approximately 200 mesh, and then freeze-dried to obtain a powder form.
  • HeLa cell lines transfected with human-derived amyloid precursor protein (APP) were cultured in DMEM medium (Cat # 11995, Gibco, USA). used.
  • the sample was added to the cell culture medium in which the cell line was cultured, then cultured at 37°C for 8 hours, and the amount of beta-amyloid secreted in the culture medium was measured.
  • the Human ⁇ -Amyloid[1-42] (A ⁇ 42) Colorimetric ELISA kit (#KHB3442; BioSource International, Inc, USA) was used. And the results are shown in Figure 1. The case where the sample was not treated was used as the control group.
  • Example 1 was found to inhibit A ⁇ 42 in a concentration-dependent manner.
  • the known MTT Cell Proliferation assay method was used. Specifically, samples of various concentrations were treated with HeLa cells cultured in the same manner as Test Example 1 for 8 hours, and then viable cells were quantified, and the results are shown in FIG. 2. The case where the sample was not treated was used as the control group.
  • Example 1 confirmed that cells almost did not die even when administered at a concentration of 5 ⁇ g/ml, confirming that it was safe for the human body. In addition, it was confirmed that the inhibition of A ⁇ 42 in Test Example 1 was not caused by apoptosis.
  • the experimental animals were male ICR mice (10 weeks old, 34 to 36 g,) adjusted to a temperature of 23 ⁇ 1°C, humidity of 60 ⁇ 10%, 12 hours of day and night, and acclimatized in an animal room for 7 days with sufficient water and regular diet. It was used in subsequent experiments.
  • the composition of Example 1 was orally administered at 100 mg/kg five times a day for three days, and on the third day of drug administration, 0.4 ⁇ g of kainic acid was directly injected into the lateral ventricle of the brain to induce epilepsy.
  • Example 1 of the present invention an animal model in which epilepsy was induced by kainic acid was used to confirm the effects of delaying the seizure latency and reducing the frequency of seizures caused by the treatment in Example 1 of the present invention.
  • stage 1 Behavioral seizure stages are identified into five stages: stage 1; facial movement, level 2; head nodding and myoclonic twitching, stage 3; forelimb clonus with lordotic posture, level 4; forelimb clonus with reared posture, level 5; There is a behavioral type of tonic-clonic seizure without postural control.
  • stage 3 forelimb clonus with lordotic posture
  • stage 3 seizure behavior occurred after kainic acid treatment was determined. It was recorded.
  • Rats treated with kainic acid were videotaped for 6 hours to measure the seizure onset time caused by kainic acid treatment, and through this, the effect of delaying the latency of seizure onset by the treatment in Example 1 was confirmed. observed.
  • SRS Spontaneous recurrent seizures

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Abstract

La présente invention concerne une composition pour la prévention ou l'amélioration de la démence sénile, et son procédé de préparation. Plus spécifiquement, la composition contient une substance chauffée, obtenue par mélange et chauffage d'Erigeron Canadensis détoxifié, de Glycyrrhiza uralensis, de Rheum rhabarbarum, de vessie à air et de vinaigre, en tant que principe actif. Selon la présente invention, la composition ne provoque pas de toxicité dans les cellules, est donc stable, peut éliminer la production de bêta-amyloïde, connue comme étant une cause de la démence sénile, en particulier de la maladie d'Alzheimer, et présente ainsi l'avantage d'être efficace pour prévenir ou traiter la démence sénile.
PCT/KR2023/003269 2022-11-29 2023-03-09 Composition pharmaceutique pour la prévention ou le traitement de la démence sénile, et son procédé de préparation WO2024117389A1 (fr)

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Citations (4)

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WO2017104706A1 (fr) * 2015-12-18 2017-06-22 国立大学法人 富山大学 Agent et composition pour induire l'expression du facteur neurotrophique dérivé du cerveau
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KR101404566B1 (ko) 2012-11-09 2014-06-11 동아대학교 산학협력단 갈색거저리 추출물을 포함하는 치매 예방 또는 치료용 조성물
KR101840451B1 (ko) 2017-09-07 2018-03-22 재단법인 통합의료진흥원 육미지황탕을 포함하는 치매 치료용 조성물

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KR102138348B1 (ko) * 2020-04-24 2020-07-28 권혁분 뇌전증의 예방 또는 치료용 조성물 및 그 제조방법

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