WO2012047063A2 - Composition pharmaceutique pour aider au traitement de la démence ou pour traiter la démence, contenant seulement un extrait d'angelica gigas nakai, seulement un extrait de feuille de ginkgo, ou un mélange d'extrait d'angelica gigas nakai et d'extrait de feuille de ginkgo - Google Patents

Composition pharmaceutique pour aider au traitement de la démence ou pour traiter la démence, contenant seulement un extrait d'angelica gigas nakai, seulement un extrait de feuille de ginkgo, ou un mélange d'extrait d'angelica gigas nakai et d'extrait de feuille de ginkgo Download PDF

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Publication number
WO2012047063A2
WO2012047063A2 PCT/KR2011/007451 KR2011007451W WO2012047063A2 WO 2012047063 A2 WO2012047063 A2 WO 2012047063A2 KR 2011007451 W KR2011007451 W KR 2011007451W WO 2012047063 A2 WO2012047063 A2 WO 2012047063A2
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Prior art keywords
extract
dementia
ginkgo biloba
angelica
donepezil
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PCT/KR2011/007451
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English (en)
Korean (ko)
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WO2012047063A3 (fr
Inventor
김명화
구세광
예인해
이한창
김강전
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제일약품주식회사
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Priority claimed from KR1020110102105A external-priority patent/KR20120038372A/ko
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Publication of WO2012047063A2 publication Critical patent/WO2012047063A2/fr
Publication of WO2012047063A3 publication Critical patent/WO2012047063A3/fr

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    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • 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
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
    • 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
    • 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

  • Angelica extract Ginkgo biloba extract alone; Or a pharmaceutical composition for treating dementia or treating dementia, including a mixture of Angelica extract and Ginkgo biloba extract
  • the present invention is a Angelica extract, Ginkgo biloba. Extracts alone; Or it relates to a pharmaceutical composition for the treatment of dementia or dementia to reduce the toxicity of dementia treatment, including a combination of Angelica extract and ginkgo biloba extract.
  • AD Alzheimer's disease
  • % Confidence interval 29--530,000 estimated at 700,000 in 2019, 1.09 million in 2030 and 2 million in 2050 (Suh GH, Journal of Korean Geriatric Psychiatry, 2002, 6: 28-35.).
  • AD Alzheimer's disease
  • SP senile plaque
  • ⁇ amyloid beta protein
  • NFTs neurofibrillary tangles
  • tacrin is known to have side effects such as hepatotoxicity, vertigo, ataxia, insomnia, gastrointestinal disorders, confusion, blood pressure disorders, anorexia, fever or nervousness.
  • LD 50 values in rodents ranged from 30-40 mg / kg, and 13-week repeated toxicity studies in rats and dogs resulted in a maximum NOEL of 1 mg / kg / day.
  • Toxicity has been confirmed (Pfizer Canada Inc., 2007), and clinical symptoms include psychiatric nervous system disorders such as muscle spasms, fatigue, insomnia and dizziness, and extracorporeal disorders or symptom such as resinous tremor and motor disorders.
  • Side effects such as nausea, vomiting and other disorders of the digestive system were noted (Dunn NR. Et al, J. Psychopharmaco I. 2000, 14: 406-82000).
  • Angelica gigas Nakai is a naturalized plant that is cultivated in Korea.
  • Korean donkey is a perennial herb. It is a perennial herb, native to Japan, 60-90 cm high, and flowers are white 8- Running at the end of branches in September, the fruit is long, flat oval, with narrow wings at the edge.
  • the root is called Angelica, and it is known to be effective for people who have no bleeding on the face, frequent dizziness, and no gloss on eyes and lips because of the effect of blood. Head weakness of the body, women's stone is excellent for menstruation, because it is often used for prenatal and postpartum diseases, and it is used to treat menstrual irregularities and abdominal pain. It is effective in the treatment of constipation due to weak gastrointestinal function-(Bae-Hwan Bae, Health Guidebook for Folk Medicine and Oriental Medicine, 2003, 102-103).
  • the known ingredients of guinea pigs include coumarine-based decursin, decursinol, nodakenetin, umbel liferon, and noda kenin ( nodakenin), beta-sitoste ( ⁇ sitosterol), angelan ⁇ I, angelan ⁇ , and so on. It has been found that isolated decusin and decusinol paralyze the rabbit harvesting intestine, have been reported to inhibit the frog extraction heart, inhibit the rabbit's breathing and lower blood pressure, and suppress the spontaneous action of mice ( Korean Journal of Pharmacognosy 1970, 1, 1: 25-32.
  • decusin is a protein phosphate It has a function of enhancing the activity of protein kinase C, and pectin polysaccharides Angelan-1, Angelan- ⁇ and the like have been disclosed as anticancer agents or immune enhancers- (Korean Patent Publication No. 1999-0031277) ).
  • Ginkgo biloba extracts have been used as drugs for thousands of years, and medicinal ginkgo biloba extracts are prepared from dried ginkgo biloba and are 24% Ginkgo-flavoneglycosides. ) And 6% terpenoids, especially the research on the neuroprotective effect of ginkgo biloba extract has been actively conducted, and many studies have been reported. Flavonoids and ginkgolides are free. Radical scavenging and antioxidant activity prevents free radicals and lipids and oxidation, and bilobalide has been shown to improve respiration in mitochondria (DeFeudis FV et al., Curr Drug Targets, 2000, 1: 25-58).
  • the present inventors have studied to find a substance that lowers the toxicity of the conventional dementia treatment and improves the dementia treatment effect, and the conventional dementia treatment in the Angelica extract, ginkgo biloba extract alone or a mixture of Angelica extract and ginkgo biloba extract When combined with the drug, pharmacokinetic parameters such as blood drug concentration and drug absorption rate are increased by reducing toxicity and increasing clinical trials (1 ⁇ 2) by reducing toxicity compared with conventional dementia treatment alone. It was confirmed that the excellent effect of treating and improving dementia by increasing the present invention was completed.
  • An object of the present invention is the Angelica extract or Ginkgo biloba extract alone; Or it is to provide a pharmaceutical composition for the treatment of dementia to attenuate the toxicity of dementia treatments, including a combination of Angelica extract and ginkgo biloba extract.
  • Angelica extract or Ginkgo biloba extract alone; Or it is to provide a pharmaceutical composition for treating dementia containing a mixture of Angelica extract and silver leaf extract as an active ingredient and a dementia treatment agent.
  • the present invention is a Angelica extract or Ginkgo biloba extract alone; Or it provides a pharmaceutical composition for the treatment of dementia, including a combination of Angelica extract and Ginkgo biloba extract, which weakens the toxicity of the dementia treatment agent.
  • the present invention is a Angelica extract or Ginkgo biloba extract; Or it provides a pharmaceutical composition for the treatment of dementia comprising a mixture of Angelica extract and silver leaf extract as an active ingredient and a dementia treatment agent.
  • FIG. 2 is a graph showing the half lethal dose LD 50 of Experimental Example 2 according to the present invention.
  • FIG 3 is a graph showing the half lethal dose LD 50 of Experimental Example 3 according to the present invention.
  • Figure 4 is a graph comparing the maximum drug concentration in the blood according to an embodiment of the present invention.
  • the present invention is the Angelica extract or Ginkgo biloba extract alone; Or it provides a pharmaceutical composition for the treatment of dementia to attenuate the toxicity of the dementia treatment agent, including a combination of Angelica extract and ginkgo leaf extract.
  • the Angelica extract or Ginkgo biloba extract may be used alone, or the Angelica extract and Ginkgo biloba extract may be used in combination.
  • composition ratio of the mixture of the Angelica extract and Ginkgo biloba extract is 1: 0.1 by weight ratio It is preferable that it is ten.
  • the composition ratio of the mixture of Angelica extract and Ginkgo biloba extract is 1: 2-6 by weight, and most preferably the composition ratio of the mixture of Angelica extract and Ginkgo biloba extract is 1: 4 by weight.
  • the donkey and ginkgo biloba can be used without limitation, such as grown, harvested or commercially available.
  • the donkey can use the whole plant, and can use the leaves, stems or roots, respectively, it is more preferable to use a double root.
  • the Angelica can be used at any stage of the growth stage, and ginkgo biloba uses 3 ⁇ 4 of ginkgo biloba.
  • the extraction solvent for extracting Angelica and Gingko biloba is preferably water, alcohol or a mixture thereof, preferably water, d-C 4 lower alcohol, or a mixture thereof, which is extracted with methanol or ethanol. More preferably, but is not limited thereto.
  • the amount of the extraction solvent is preferably 2 to 30 times the dry weight of Angelica and Ginkgo biloba, more preferably 20 times, but is not limited thereto.
  • the method of extracting the Angelica extract and Ginkgo biloba extract is a method using an extraction device such as hot water extraction, dipping extraction, supercritical extraction, subcritical extraction, high temperature extraction, high pressure extraction, reflux cooling extraction and ultrasonic extraction or XAD and HP Conventional extraction methods in the art can be used, such as using an adsorptive resin containing -20, and is preferably heated, reflux extraction or phase extraction from, but is not limited thereto.
  • Extraction times of the sugar ear extract and ginkgo biloba extract is preferably 1 to 5 times, more preferably three times repeated extraction is not limited thereto. It can be extracted once to five times by the ultrasonic extraction method.
  • the temperature during extraction is preferably 10 ° C ⁇ 100 ° C and more preferably room temperature, but is not limited thereto.
  • the extraction time is preferably 1 hour-24 hours, more preferably 3 hours-7 days, but is not limited thereto.
  • the vacuum concentration is preferably a vacuum rotary evaporator, but is not limited thereto.
  • the drying is preferably reduced pressure drying, vacuum drying, boiling drying, spray drying, room temperature drying or lyophilization, but is not limited thereto.
  • the composite composition according to the present invention is concentrated under reduced pressure at a temperature of 6 70 ° C. It can be prepared in powder form by making soft lead extract, lyophilizing or drying using spray dryer or oil bed granulator.
  • the composition of the donepezil, Angelica extract and ginkgo biloba extract according to the present invention is the maximum blood drug according to the dosage in the group to which the combination composition is administered than when using the donepezil alone It is very useful as a pharmaceutical composition for the treatment of dementia by showing the effect of increasing the time to reach the concentration, increasing the maximum blood drug concentration, increasing the drug residence time in the blood, and significantly increasing the absorption rate and absorption rate of the drug. It was confirmed that it can be used (see Experimental Example 6).
  • the present invention is the Angelica extract or Ginkgo biloba extract alone; Or it provides a pharmaceutical composition for the treatment of dementia containing a mixture of Angelica extract and ginkgo biloba extract and the dementia treatment as an active ingredient.
  • the dementia treatment agent may be prepared and used, but may be commercially available in the art, but is not limited thereto.
  • the composite composition may be used alone or in combination with an extract for treating dementia, and the mixture of the Angelica extract and Ginkgo biloba extract may be used in combination with the treatment for dementia. have.
  • the extract of Angelica extract or Ginkgo biloba may be prepared and used by the method described above for the Angelica extract and Ginkgo biloba extract, and commercially available ones may be used, but are not limited thereto.
  • the ginkgo biloba extract may be used in combination with the Angelica extract, and in this case, the mixing ratio of the ginkgo biloba extract is preferably 1: 0.1-10 by weight ratio. More preferably, the composition ratio of the mixture of Angelica extract and Ginkgo biloba extract is 1: 2-6 in an increase ratio, and most preferably, the composition ratio of the mixture of Angelica extract and Ginkgo biloba extract is 1: 4 in weight ratio.
  • the dementia treatment agent is preferably donepezil, galantamine, memantine, rivastigmine and tacrine, and more preferably may be donepezil, but is not limited thereto.
  • the composition according to the present invention is a conventional extract for treatment of dementia, Angelica extract, Ginkgo biloba extract alone or; By adding a combination of Angelica extract and Ginkgo biloba extract, the toxicity is reduced compared to the case of using the existing dementia treatment alone, resulting in an increase in the anti-numerical dose ⁇ 3 ⁇ 4 0 ) and pharmacokinetic parameters such as blood drug concentration and blood drug residence time.
  • it can be useful as a treatment for dementia because it shows an excellent dementia treatment effect such as improvement of clinical symptoms such as tremor (muscle cramps), depression, ataxia and stool.
  • Angelica extract Ginkgo biloba extract alone of the present invention
  • the composition comprising the Angelica extract and the silver leaf extract preferably comprises from 0.1 to 80% by weight based on the total weight of the composition, but is not limited thereto.
  • compositions of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of a medicament.
  • compositions according to the present invention powders, granules tablets, caps according to a conventional method, respectively
  • compositions of the present invention may be used in the form of oral dosage forms such as suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions.
  • the carriers, excipients and diluents which may be included in the compositions of the present invention include lactose.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may include at least one excipient in the composition of the present invention, for example, starch, calcium carbonate.
  • Oral liquid preparations include suspensions, liquid solutions, emulsions, and syrups.
  • excipients for example, wetting agents, sweeteners, fragrances, and preservatives may be included.
  • Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories.
  • Non-aqueous solvents and suspending agents may be used such as propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • a suppository base witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol gelatin, etc. may be used.
  • composition of the present invention may be administered orally or parenterally, for example, orally, sublingually, nasal, rectally or subcutaneously.
  • composition of the present invention depends on the age, condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, but may be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention is normal (standard weight
  • 60 kg may be administered in divided doses 1 to 3 times a day within the range of 10-1500 mg, but is not necessarily limited thereto and the dosage does not in any way limit the scope of the present invention.
  • the Angelica used in this experiment was Angelica Gigas Radix, which was collected from Pyeongchang, Gangwon-do, and 100% of Angelica was added 50% ethane to 2.7 and water bath (East-West Science DS-SWB).
  • the filtrate was filtered under reduced pressure using a filter paper to obtain a concentrate using a vacuum rotary evaporator (BUCHI Rotavapor R-144, swizerland), which was then lyophilized. Dried to obtain a powder.
  • Angelica obtained 32 g of lyophilized extract in a yield of 32 ⁇ 3 ⁇ 4.
  • the freeze-dried extract powder was dissolved in distilled water at a concentration of 10 mg / m ⁇ , and stored in a -20 ° C copper chamber blocked from light and denaturation.
  • Ginkgo biloba extract (Ginkgo biloba extract) was used as a product sold by the Indena (Indena), and the extract and the ginkgo biloba extract prepared in Example 1 is common in weight ratio as shown in Table 1 below Combined, the mixture was prepared using the Angelica extract and Ginkgo biloba extract for toxicity testing.
  • the Donepezil and Angelica extract complex composition was dissolved in distilled water 50 to prepare a complex composition solution of Donepezil and Angelica extract, and donepezil alone was dissolved in distilled water 50, donepezil solution.
  • distilled water 50 To prepare a complex composition solution of Donepezil and Angelica extract, and donepezil alone was dissolved in distilled water 50, donepezil solution.
  • Donepezil (HC1 ⁇ 3 ⁇ 40) was used as a product sold by Cheil Pharm.
  • the powder of Angelica Extract, Donepezil and Ginkgo biloba (Indana) extract of Example 1 were light brown, white and Off-white, isolated from light and denaturation 4, -10 ° C And stored at ⁇ 10 ° C. before use.
  • the mouse is donepezil alone administration group, the composite composition prepared in Example 2 ⁇ was mixed with donepezil as shown in Table 3 below, dissolved in distilled water 20, respectively, divided into groups of 50, 100, 200 and 400 mg / kg, and the experiment was carried out.
  • Each group was administered by kg, and the group administered only saline was labeled S1, the group using 60 mg / kg of donepezil was labeled S2, the group using 40 mg / kg of donepezil was labeled S3, The group using 20 mg / kg of petroleum was designated as S4.
  • mice died (100%) within 1 day after administration.
  • mice died in all the groups that received the combination composition of Donepezil 60 mg / kg, Angelica extract and Ginkgo biloba extract, but increased dose of Donepezil 40 mg / kg, Angelica extract and Ginkgo biloba extract
  • the weight of Donepezil 40 mg / kg, Angelica extract and Ginkgo biloba extract were 50, 100 and 200 mg / kg, respectively.
  • three rats 60%) died.
  • mice In the group receiving 20 mg / kg of donepezil alone, two (40%) mice were killed. One (20%) or two (40 mice died) in the composite composition of 20 mg / kg of Donepezil, Angelica extract, and Ginkgo biloba extracts weighing 50, 100 and 200 mg / kg, respectively. There was no death in the case of the composite composition of Donepezil 20 mg / kg, Angelica extract and Ginkgo biloba extract, each weighing 400 mg / kg.
  • the result of calculating the half lethal dose (LD 50 ) was 21.17 mg / kg of the donepezil monotherapy group, whereas the composition ratio of the donepezil, Angelica extract and ginkgo biloba extract was 1
  • the 50-, 100-, 200-, and 400-mg / kg-administered group had a half lethal dose (LD 50 ) of 29.99, 30.00, 29.99, and 38.71 mg / kg, respectively.
  • the composite composition of the leaf extract 400 mg / kg administration group was confirmed to be the least toxic (see Fig.).
  • the composite composition of donepezil, Angelica extract and ginkgo biloba extract of the present invention is very effective in reducing toxicity than the group administered with donepezil alone, so as to aid the treatment of dementia and to treat dementia. It can be usefully used.
  • ARICEPTRDT donepez i 1 hydrochloride Rapidly Disintegrating Tablets 5 and 10 mg Cholinesterase Inhibitor.
  • the highest dose was selected as 60 mg g / kg of nepezil, based on the previous dose of 45.2 mg / kg of the hepatic dose (LD 50 ) of the male mouse and 40 and 20 mg. Experiments were performed with / kg set to medium and low dose groups. The results are shown in Table 7 and FIG. 2.
  • the composite composition of the donepezil, Angelica extract and ginkgo biloba extract of the present invention has a very excellent effect of significantly reducing the toxicity of donepezil (1 50 is significantly increased), so as a pharmaceutical composition for preventing and treating dementia. It can be usefully used.
  • Angelica extract Ginkgo biloba extract (1: 4) on the lethal dose of donepezil
  • mice died on the day of administration, and donepezil 60mg / kg + all Angelica extract: Ginkgo biloba extract (1: 4) group composition, donepezil 40mg / kg + sugar ear extract: Ginkgo biloba extract (1: 4) All experimental animals (5/5; 100%) also died within 24 hours after administration of the 50 and 100 mg / kg combination compositions.
  • donepezil 40 mg / kg + Angelica extract Ginkgo biloba extract (1: 4)
  • donepezil 40 mg / kg + Angelica extract Ginkgo biloba extract (1: 4)
  • donepezil 40 mg / kg + Angelica extract Ginkgo biloba extract (1: 4)
  • the composite composition of the donepezil, Angelica extract and ginkgo biloba extract of the present invention has a very excellent effect of significantly reducing the toxicity of donepezil (1 50 is significantly increased) as a pharmaceutical composition for preventing and treating dementia. It can be usefully used.
  • mice After performing Experimental Example 2, the surviving mice were examined for the clinical symptoms associated with all donepezil administration, such as tremor (muscle cramps), depression / exercise and stool, and are shown in Table 7 below.
  • the clinical symptoms are weak depending on the extent of the symptoms; 1+ , medium; 2+ and severe; 3+, and b ND when it is impossible to measure due to death.
  • the donepezil 20 mg / kg alone group showed a weaker level of progression (2+) than (3+), and donepezil (40 mg / kg).
  • Donepezil (20 mg / kg), Angelica (400 mg / kg), and Ginkgo biloba (400 mg / kg) combination composition the severity of symptoms decreased from 3+ to 2+ and 3+ to 1+, respectively. It was.
  • a combination of donepezil (40 mg / kg) or donepezil (20 mg / kg), donkey and ginkgo biloba (50, 100, 200 and 400 mg / kg, respectively) was used in the numbers indicating depression and ataxia. Depression and ataxia were shown in the group treated with the composition, but in the case of 50 mg / kg, the symptom level was 2+ for the day, whereas in the case of 100 mg / kg, the symptom was observed for 3 days. In the case of 200 mg / kg and 400 mg / kg, the degree of symptom was 1+ for 2 days.
  • the composite composition of the donepezil, Angelica extract and ginkgo biloba extract of the present invention is not only the onset of symptoms but also the extent of symptoms in tremor (muscular cramps) and depression / ataxia than the donepezil alone group. Since it is excellent in the effect that can be usefully used as a pharmaceutical composition for the prevention and treatment of dementia.
  • the absorption to infinity concentration-time curve area was 602.01 ng / ⁇ , which increased the absorption rate of the drug by 37% compared to the donepezil alone group, and the half-life was 10.7 hours, about 25% compared to the donepezil alone group. Increased the rate of absorption of the drug.
  • the mean residence time of the drug was 16 and 2 hours, 2.6 hours, compared to the donepezil alone group. It was confirmed that the liver (20%) was long.
  • the composite composition of the donepezil, Angelica extract and ginkgo biloba extract of the present invention increases the blood drug concentration, increases the absorption rate of the drug, and also increases the drug residence time than the group administered with donepezil alone. Since it is very excellent it can be usefully used as a pharmaceutical composition for the prevention and treatment of dementia.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • Magnesium stearate 2 mg A capsule is prepared by mixing the above ingredients according to a conventional capsul-preparation method and filling it into 3 ⁇ 4 capsule of gelatin. : 168>

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Abstract

La présente invention porte sur une composition pharmaceutique pour aider au traitement de la démence ou pour traiter la démence, contenant seulement un extrait d'Angelica gigas Nakai, seulement un extrait de feuille de ginkgo, ou un mélange d'un extrait d'Angelica gigas Nakai et d'un extrait de feuille de ginkgo. Selon la présente invention, le seul extrait d'Angelica gigas Nakai, le seul extrait de feuille de ginkgo, ou le mélange d'un extrait d'Angelica gigas Nakai et d'un extrait de feuille de ginkgo réduit la toxicité et augmente la dose létale médiane (DL50) pour réduire la toxicité d'un agent thérapeutique de la démence, et augmente des valeurs pharmacodynamiques en tant qu'assistant de l'agent thérapeutique de la démence, et peut ainsi être utile dans une composition pharmaceutique pour aider au traitement de la démence ou pour traiter la démence.
PCT/KR2011/007451 2010-10-08 2011-10-07 Composition pharmaceutique pour aider au traitement de la démence ou pour traiter la démence, contenant seulement un extrait d'angelica gigas nakai, seulement un extrait de feuille de ginkgo, ou un mélange d'extrait d'angelica gigas nakai et d'extrait de feuille de ginkgo WO2012047063A2 (fr)

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KR10-2010-0098349 2010-10-08
KR20100098349 2010-10-08
KR10-2011-0102105 2011-10-06
KR1020110102105A KR20120038372A (ko) 2010-10-08 2011-10-06 당귀 추출물, 은행엽 추출물 단독； 또는 당귀 추출물 및 은행엽 추출물의 혼합물을 포함하는 치매 치료보조용 또는 치매치료용 약학적 조성물

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KR20000071673A (ko) * 1999-04-13 2000-11-25 이희설 하이드록시신남산 유도체 또는 이를 포함하는 당귀추출물을 함유하는 치매 예방 및 치료용 조성물
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