WO2002074295A1 - A composition for the prophylaxis or treatment of senile dementia - Google Patents
A composition for the prophylaxis or treatment of senile dementia Download PDFInfo
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- WO2002074295A1 WO2002074295A1 PCT/KR2002/000449 KR0200449W WO02074295A1 WO 2002074295 A1 WO2002074295 A1 WO 2002074295A1 KR 0200449 W KR0200449 W KR 0200449W WO 02074295 A1 WO02074295 A1 WO 02074295A1
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- curcumin
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- senile dementia
- preventing
- curcuma aromatica
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
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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
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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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
Definitions
- the present invention relates to a composition for the prophylaxis and treatment of senile dementia, which comprises Curcumin or an extract of Curcuma aromatica SALISB. containing the Curcumin.
- Alzheimer's disease one of the most common senile dementia, of which major causative factors are accumulation of beta-amyloid(A ⁇ ⁇ _ 2 ) in cerebrum and neurotoxicity derived therefrom (Selkoe, Annual Reviews in Neuroscience, 17, 489-517 (1994)).
- beta-amyloid A ⁇ ⁇ _ 2
- neurotoxicity derived therefrom
- Curcuma aromatica SALISB is a pharmaceutical plant that has been long used for treatment of cholelithiasis, infectious hepatitis, hepatic pain and other disorder and as an analgesic and a diuretic.
- Curcumin of the formula (I) below one of ingredients extracted from Curcuma aromatica SALISB., is known to have several advantageous effects including a liver function strengthening effect, an antibacterial effect of inhibiting pylori bacteria which are causative bacteria of gastric ulcer, a cholagogic effect to promote bile secretion, or diuretic function:
- SALISB or Curcumin in preventing and treating senile dementia.
- Another object of the present invention is to provide a functional food for preventing senile dementia.
- an aspect of the present invention provides a pharmaceutical composition for preventing and treating senile dementia, comprising Curcumin or a pharmaceutically acceptable salt thereof as an effective ingredient.
- a pharmaceutical composition for preventing and treating senile dementia which comprises an extract of Curcuma aromatica SALISB. containing Curcumin, and a pharmaceutically acceptable carrier.
- a method of preventing and treating senile dementia by administering a therapeutically effective amount of Curcumin or a pharmaceutically acceptable salt thereof.
- a method of preventing and treating senile dementia by administering a therapeutically effective amount of an extract of Curcuma aromatica SALISB. containing Curcumin.
- a functional food for preventing senile dementia comprising Curcumin as an effective ingredient.
- a functional food for preventing senile dementia comprising an extract of Curcuma aromatica SALISB. as an effective ingredient.
- FIG. 1 is a graph showing the results of passive avoidance tests conducted on mice, which was administrated by an extract of Curcuma aromatica SALISB. in different amounts;
- FIG. 1 is a graph showing the results of passive avoidance tests conducted on mice, which was administrated by Curcumin in different amounts.
- Curcumin can be extracted from Curcuma aromatica SALISB. by the known method described in Rasmussen HB, et al., Planta Med., 66(4), 396-8 (2000), synthesized by the known methods described in various references including the Merck Index, or can be commercially available.
- the Curcumin is generally prepared in various forms of pharmaceutically acceptable salts known in the art, including inorganic salts such as sodium salts, potassium salts, magnesium salts or calcium salts; organic salts of lysine, ethanol amine, N,N'-dibenzylethylene diamine and ⁇ -tocopherol; and esters of triterpene alcohols or plant sterols such as cycloartol ("oryzanol').
- inorganic salts such as sodium salts, potassium salts, magnesium salts or calcium salts
- organic salts of lysine, ethanol amine, N,N'-dibenzylethylene diamine and ⁇ -tocopherol such as esters of triterpene alcohols or plant sterols such as cycloartol ("oryzanol').
- Curcumin is also contained in Curcuma aromatica SALISB.
- the extract can be used in the form of an extract of Curcuma aromatica SALISB.
- the extract can be prepared by a general method using a polar solvent, e.g., water; a low-grade alcohol such as methanol or ethanol; an organic solvent such as methylene chloride; or mixtures thereof.
- a polar solvent e.g., water
- a low-grade alcohol such as methanol or ethanol
- an organic solvent such as methylene chloride
- rhizomes of Curcuma aromatica SALISB. can be extracted with boiling water, or extracted with an organic solvent at 5 to 80°C (Celsius), preferably 30 to 55°C, for 30 minutes to 55 hours, preferably 30 minutes to 12 hours.
- the resulted extract contains 0.01 to 3% by weight of Curcumin based on total weight of the extract.
- To make the extract into powder it may be decompressed and dried.
- Curcumin or an extract of Curcuma aromatica SALISB exhibits little toxicity in tests using mice, such as acute toxicity, nor side effects harmful to liver function.
- a pharmaceutical composition for preventing and treating senile dementia can be prepared by mixing Curcumin or an extract of Curcuma aromatica SALISB. with a suitable carrier or an excipient which is pharmaceutically acceptable, or by diluting with a diluent.
- Suitable examples of the carrier, the excipient and the diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, glucose, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, amorphous cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
- the pharmaceutical composition may further include a filler, an anti-flocculating agent, a lubricant, a wetting agent, a flavor, an emulsifier, an antiseptic and the like.
- the pharmaceutical composition of the present invention can be formulated by methods which are well known to those of skilled in the art so as to provide fast, continuous or delayed emission of the active ingredient upon administration into a mammal.
- Formulations may be in the form of a pellet, a tablet, powder, a sachet, an elixir, a suspension, an emulsion, a solution, a syrup, an aerosol, a soft or hard gelatin capsule, a sterile injection or sterile powder.
- the pharmaceutical composition can be administered by various routes such as orally, percutaneously, subcutaneously, and intravenously.
- Curcumin may be administered at a dose of about 0.1 to 100 mg/kg of body weight per day
- the extract of Curcuma aromatica SALISB. may be administered at a dose of about 1 to 1000 mg/kg of body weight per day.
- the dose can be administrated totally once, or divisionally several times a day. It will be understood, however, the specific dose level of the active ingredient for any particular patient will be depend upon a variety of factors including route of administration, the age, sex, body weight, severity of the disease, etc., and thus the above-noted dose level does not limit the scope of the present invention in any way.
- Curcumin or an extract of Curcuma aromatica SALISB can be added into a dietary supplementary or beverage for the purpose of preventing senile dementia.
- the present invention also provides a functional food or drinkable composition for preventing senile dementia comprising an effective amount of Curcumin or an extract of Curcuma aromatica SALISB.
- the foods to which the Curcumin or the extract of Curcuma aromatica SALISB. according to the present invention can be added for the purpose of preventing senile dementia include a variety of foods, drinkables, gums, teas, vitamin complexes and health-supplementary foods.
- the functional food having a dementia preventing effect can be prepared by adding the Curcumin or extract of Curcuma aromatica SALISB.
- the content of the Curcumin contained in the finally produced food or drinkables is preferably in the range of 0.001 to 0.1% by weight, and the content of the extract of Curcuma aromatica SALISB. contained in the finally produced food or drinkables is preferably in the range of 0.5 to 10% by weight.
- Reference Example 1 Intracerebro ventricular (icy) injection ⁇ .%5 ⁇ gl5 ⁇ & beta-amyloid (1-42 amino acids) was injected intracerebroventricularly by using a 50/t Hamilton Syringe fitted with a 26-gauge needle until the tip of the needle was inserted 2.4 mm deep into the bregma of each mouse, according to the method described in Laursen & Belknap, J Pharmacol. Methods, 16, 355-357 (1986). For mice in a sham group, physiological saline in an equivalent amount was injected.
- Reference Example 2 Passive avoidance test
- a passive avoidance test was carried out by the following method described in Song et al., J. Neurochem, 71, 875-878 (1998).
- a passive avoidance chamber consisting of an illuminated compartment and a dark compartment, in which means to deliver electrical shock are constructed on the bottom thereof.
- an electrical shock (0.25 mA) was applied to the mouse for 1 second.
- the mouse was again placed in the illuminated compartment and the latency to enter the dark compartment, that is, a passive avoidance response time, was measured.
- the maximum limit of time was set to 300 seconds. If the mouse did not enter the dark compartment even after 300 seconds, the latency of 300 seconds was determined as the passive avoidance response time.
- Preparation Example Preparation of extract of Curcuma aromatica SALISB. 300g of the root of Curcuma aromatica SALISB. (commercially available from Jeonghan Co., Ltd.), which was carefully selected and cut into small pieces, was added to 21 of water, followed by extracting at 100°C for 4 hours. The extracted product was collected, and moisture was removed therefrom using a decompressed reflux cooling tube, and then was completely dried using a freeze-dryer, yielding 25 g of extract powder of Curcuma aromatica SALISB.
- Example 1 Prevention of senile dementia by the extract of Curcuma aromatica SALISB.
- mice of 4-5 weeks old, weighing 20 to 25 g were divided into 4 groups composed of each 10 mice.
- the extract of Curcuma aromatica SALISB. prepared in the Preparation Example, was dissolved in physiological saline and then orally administered five times in amounts of 0.25 g/kg and 0.5 g/kg (corresponding to 7.5 mg/kg and 15 mg/kg of Curcumin), respectively, at intervals of 10 hours.
- an oral syringe for mouse was used for the oral administration of the extract.
- after administering the extract of Curcuma aromatica SALISB was administered.
- beta-amyloid (aa 1-42) (available from American Peptide Co.) was intracerebroventricularly injected into each mouse according to the method described in Reference Example 1.
- physiological saline instead of the extract of Curcuma aromatica SALISB.
- physiological saline instead of beta-amyloid
- beta-amyloid was intracerebroventricularly injected.
- mice in a control group physiological saline, instead of the extract of Curcuma aromatica SALISB., was orally administered in the same manner as described above, and beta-amyloid was then intracerebroventricularly injected in the same manner as described above.
- Curcumin available from Sigma Co.
- mice in two test groups Curcumin (available from Sigma Co.) was dissolved in corn oil and then orally administered five times in amounts of 10 mg/kg and 100 mg/kg, respectively, at intervals of 10 hours.
- the oral administration of Curcumin was conducted by using an oral syringe for mouse.
- 1.85 ⁇ g (5 l) of beta-amyloid (aa 1-42) was intracerebroventricularly injected into each mouse according to the method described in Reference Example 2.
- mice in a sham group corn oil, instead of Curcumin, was orally administered, and physiological saline, instead of beta-amyloid, was intracerebroventricularly injected.
- physiological saline, instead of Curcumin was orally administered in the same manner as described above, and beta-amyloid was then intracerebroventricularly injected in the same manner as described above.
- FIG. 2 shows the results of the test, expressed with an average value of latencies for 10 mice.
- the mice in the control group showed a significant reduction in passive avoidance response time (PO.001) compared with those in the sham group
- the mice of the test groups administered with 10 g/kg and 100 g/kg of Curcumin, respectively showed significant increases in passive avoidance response time (P ⁇ 0.05 for mice administered with 10 mg/kg Curcumin and PO.01 for mice administered with 100 mg/kg Curcumin).
- the passive avoidance response time increased in a Curcumin-concentration dependent way. It was confirmed from these results that Curcumin suppressed memory impairment due to accumulation of beta-amyloid.
- Test Example 1 Oral toxicity test for the extract of Curcuma aromatica SALISB.
- mice Each 20 of female and male ICR mice of 4 weeks old, were bred at an animal room with conditions of 22+ 3 ° C in temperature, 50+ 10% in relative humidity and 150-300 Lux in light intensity, for one week, and then divided into 4 groups each having 5 female mice and 5 male mice.
- the extract of Curcuma aromatica SALISB. prepared according to Preparation Example was dissolved in physiological saline and then orally administered once in amounts of 300, 1,000 and 3,000 mg/kg, respectively.
- a change in general symptoms and outbreak of dead animals were observed.
- 7 days after administration the mice were killed and anatomized, following by examining their viscera with the naked eye.
- On and after administration by measuring a change in body weight everyday, it was determined whether the animals showed a reduction in body weight due to the administered extract of Curcuma aromatica SALISB .
- Hard gelatin capsule formulation cellulose 15 mg of isoflavone, 2.5 mg of Ginkgo biloba extract, 2 mg of extract of dried seed of Zizyphus spinosa, 0.25 mg of vitamin Bi, 0.3 mg of vitamin B 2 , 0.0025 mg of vitamin B 3 and 2.5 mg of magnesium stearate were completely mixed, followed by filling into a hard gelatin capsule, thereby forming a hard gelatin capsule formulation.
- composition according to the present invention which comprises Curcumin or an extract of Curcuma aromatica SALISB. as an effective ingredient, can be advantageously used for preventing and treating senile dementia.
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Abstract
According to the present invention, provided are a pharmaceutical composition for preventing and treating senile dementia and a functional food for preventing senile dementia, comprising Curcumin or an extract of Curcuma aromatica SALISB. containing the Curcumin. The pharmaceutical composition and the functional food can be advantageously used in preventing and/or treating senile dementia.
Description
A COMPOSITION FOR THE PROPHYLAXIS OR TREATMENT OF SENILE
DEMENTIA
Field of The Invention
The present invention relates to a composition for the prophylaxis and treatment of senile dementia, which comprises Curcumin or an extract of Curcuma aromatica SALISB. containing the Curcumin.
Background of The Invention
Recently, as the proportion of aged people has sharply increased, incidence of senile dementia associated with aging has become an extremely serious social problem. In spite of a high incidence of senile dementia, since there are few useful therapeutic and preventive agents thereof up to now, huge socioeconomic problems associated with the disease have been raised.
It is known that Alzheimer's disease, one of the most common senile dementia, of which major causative factors are accumulation of beta-amyloid(Aβ ι_ 2) in cerebrum and neurotoxicity derived therefrom (Selkoe, Annual Reviews in Neuroscience, 17, 489-517 (1994)). For prevention and treatment of Alzheimer's disease, attempts to develop agents for inhibiting toxicity of beta-amyloid known as a primary causative material of Alzheimer's disease have been continuously made. So far few effective therapeutic agents have, however, been developed.
Curcuma aromatica SALISB. is a pharmaceutical plant that has been long used for treatment of cholelithiasis, infectious hepatitis, hepatic pain and other disorder and as an analgesic and a diuretic. In particular, Curcumin of the formula (I) below, one of ingredients extracted from Curcuma aromatica SALISB., is known to have several advantageous effects including a liver function strengthening effect, an antibacterial
effect of inhibiting pylori bacteria which are causative bacteria of gastric ulcer, a cholagogic effect to promote bile secretion, or diuretic function:
(I) However, there have been no reports on effects of Curcuma aromatica
SALISB. or Curcumin in preventing and treating senile dementia.
Object of The Invention
It is therefore an object of the present invention to provide a pharmaceutical composition and a method for preventing and treating senile dementia.
Another object of the present invention is to provide a functional food for preventing senile dementia.
Summary of The Invention
To accomplish the objects, an aspect of the present invention provides a pharmaceutical composition for preventing and treating senile dementia, comprising Curcumin or a pharmaceutically acceptable salt thereof as an effective ingredient. In another aspect of the present invention, there is provided a pharmaceutical composition for preventing and treating senile dementia, which comprises an extract of Curcuma aromatica SALISB. containing Curcumin, and a pharmaceutically acceptable carrier.
In a further aspect of the present invention, there are provided uses of Curcumin or a pharmaceutically acceptable salt thereof in preparing a pharmaceutical composition for preventing and treating senile dementia.
In a still further aspect of the present invention, there are provided uses of an extract of Curcuma aromatica SALISB. containing Curcumm in preparing a pharmaceutical composition for preventing and treating senile dementia.
In a yet another aspect of the present invention, there is provided a method of preventing and treating senile dementia by administering a therapeutically effective amount of Curcumin or a pharmaceutically acceptable salt thereof.
In a further aspect of the present invention, there is provided a method of preventing and treating senile dementia by administering a therapeutically effective amount of an extract of Curcuma aromatica SALISB. containing Curcumin. To accomplish another object of the present invention, there is provided a functional food for preventing senile dementia, comprising Curcumin as an effective ingredient.
In a further aspect of the present invention, there is provided a functional food for preventing senile dementia, comprising an extract of Curcuma aromatica SALISB. as an effective ingredient.
Brief Description of The Drawings
i
FIG. 1 is a graph showing the results of passive avoidance tests conducted on mice, which was administrated by an extract of Curcuma aromatica SALISB. in different amounts; and
FIG. 1 is a graph showing the results of passive avoidance tests conducted on mice, which was administrated by Curcumin in different amounts.
Detailed Description of The Invention
The present invention will now be described in detail.
Curcumin can be extracted from Curcuma aromatica SALISB. by the known
method described in Rasmussen HB, et al., Planta Med., 66(4), 396-8 (2000), synthesized by the known methods described in various references including the Merck Index, or can be commercially available.
The Curcumin is generally prepared in various forms of pharmaceutically acceptable salts known in the art, including inorganic salts such as sodium salts, potassium salts, magnesium salts or calcium salts; organic salts of lysine, ethanol amine, N,N'-dibenzylethylene diamine and α-tocopherol; and esters of triterpene alcohols or plant sterols such as cycloartenol ("oryzanol').
Since the Curcumin is also contained in Curcuma aromatica SALISB., it can be used in the form of an extract of Curcuma aromatica SALISB. The extract can be prepared by a general method using a polar solvent, e.g., water; a low-grade alcohol such as methanol or ethanol; an organic solvent such as methylene chloride; or mixtures thereof. For example, rhizomes of Curcuma aromatica SALISB. can be extracted with boiling water, or extracted with an organic solvent at 5 to 80°C (Celsius), preferably 30 to 55°C, for 30 minutes to 55 hours, preferably 30 minutes to 12 hours. The resulted extract contains 0.01 to 3% by weight of Curcumin based on total weight of the extract. To make the extract into powder, it may be decompressed and dried.
Curcumin or an extract of Curcuma aromatica SALISB. containing the Curcumin effectively prevents memory impairment, thereby exhibiting preventive and therapeutic effects of senile dementia, particularly in Alzheimer's disease models in which memory impairment is caused by directly injecting beta-amyloid into a cerebral ventricle of mouse.
While having the above-stated effectiveness, Curcumin or an extract of Curcuma aromatica SALISB. exhibits little toxicity in tests using mice, such as acute toxicity, nor side effects harmful to liver function.
A pharmaceutical composition for preventing and treating senile dementia can be prepared by mixing Curcumin or an extract of Curcuma aromatica SALISB. with a suitable carrier or an excipient which is pharmaceutically acceptable, or by diluting
with a diluent. Suitable examples of the carrier, the excipient and the diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, glucose, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, amorphous cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The pharmaceutical composition may further include a filler, an anti-flocculating agent, a lubricant, a wetting agent, a flavor, an emulsifier, an antiseptic and the like. The pharmaceutical composition of the present invention can be formulated by methods which are well known to those of skilled in the art so as to provide fast, continuous or delayed emission of the active ingredient upon administration into a mammal. Formulations may be in the form of a pellet, a tablet, powder, a sachet, an elixir, a suspension, an emulsion, a solution, a syrup, an aerosol, a soft or hard gelatin capsule, a sterile injection or sterile powder.
The pharmaceutical composition can be administered by various routes such as orally, percutaneously, subcutaneously, and intravenously. Curcumin may be administered at a dose of about 0.1 to 100 mg/kg of body weight per day, and the extract of Curcuma aromatica SALISB. may be administered at a dose of about 1 to 1000 mg/kg of body weight per day. The dose can be administrated totally once, or divisionally several times a day. It will be understood, however, the specific dose level of the active ingredient for any particular patient will be depend upon a variety of factors including route of administration, the age, sex, body weight, severity of the disease, etc., and thus the above-noted dose level does not limit the scope of the present invention in any way.
In the meantime, Curcumin or an extract of Curcuma aromatica SALISB. can be added into a dietary supplementary or beverage for the purpose of preventing senile dementia. Thus, the present invention also provides a functional food or drinkable composition for preventing senile dementia comprising an effective amount of Curcumin or an extract of Curcuma aromatica SALISB. Examples of the foods to
which the Curcumin or the extract of Curcuma aromatica SALISB. according to the present invention can be added for the purpose of preventing senile dementia include a variety of foods, drinkables, gums, teas, vitamin complexes and health-supplementary foods. The functional food having a dementia preventing effect can be prepared by adding the Curcumin or extract of Curcuma aromatica SALISB. according to the present invention into a source material of the food during the manufacture of the food, or by mixing the same with a final product. Here, the content of the Curcumin contained in the finally produced food or drinkables is preferably in the range of 0.001 to 0.1% by weight, and the content of the extract of Curcuma aromatica SALISB. contained in the finally produced food or drinkables is preferably in the range of 0.5 to 10% by weight.
The present invention will be illustrated in more detail with reference to the following Examples. The following are understood to be illustrative only and are not intended to limit the scope of the present invention in any way.
All percentages of solid/solid, liquid/liquid and liquid/solid mixtures referred to in the following examples will be based on percents (%) by weight/weight, volume/volume and weight/volume, respectively, and all reactions of the examples are carried out at room temperature, unless specified otherwise.
Reference Example 1 : Intracerebro ventricular (icy) injection \.%5βgl5μ& beta-amyloid (1-42 amino acids) was injected intracerebroventricularly by using a 50/t Hamilton Syringe fitted with a 26-gauge needle until the tip of the needle was inserted 2.4 mm deep into the bregma of each mouse, according to the method described in Laursen & Belknap, J Pharmacol. Methods, 16, 355-357 (1986). For mice in a sham group, physiological saline in an equivalent amount was injected.
Reference Example 2: Passive avoidance test
To evaluate the learning ability and memory of mice, a passive avoidance test was carried out by the following method described in Song et al., J. Neurochem, 71, 875-878 (1998). In this test, it was used a passive avoidance chamber consisting of an illuminated compartment and a dark compartment, in which means to deliver electrical shock are constructed on the bottom thereof. First, a mouse was placed into the illuminated chamber, and then as soon as the mouse entered the dark compartment, an electrical shock (0.25 mA) was applied to the mouse for 1 second. After twenty-four hours of the training, the mouse was again placed in the illuminated compartment and the latency to enter the dark compartment, that is, a passive avoidance response time, was measured. The maximum limit of time was set to 300 seconds. If the mouse did not enter the dark compartment even after 300 seconds, the latency of 300 seconds was determined as the passive avoidance response time.
Preparation Example: Preparation of extract of Curcuma aromatica SALISB. 300g of the root of Curcuma aromatica SALISB. (commercially available from Jeonghan Co., Ltd.), which was carefully selected and cut into small pieces, was added to 21 of water, followed by extracting at 100°C for 4 hours. The extracted product was collected, and moisture was removed therefrom using a decompressed reflux cooling tube, and then was completely dried using a freeze-dryer, yielding 25 g of extract powder of Curcuma aromatica SALISB.
Example 1 : Prevention of senile dementia by the extract of Curcuma aromatica SALISB.
40 ICR mice of 4-5 weeks old, weighing 20 to 25 g, were divided into 4 groups composed of each 10 mice. For mice of two test groups, the extract of Curcuma aromatica SALISB. prepared in the Preparation Example, was dissolved in
physiological saline and then orally administered five times in amounts of 0.25 g/kg and 0.5 g/kg (corresponding to 7.5 mg/kg and 15 mg/kg of Curcumin), respectively, at intervals of 10 hours. Here, an oral syringe for mouse was used for the oral administration of the extract. Also, after administering the extract of Curcuma aromatica SALISB. twice (19 hours after starting administration), 1.85 βg (5 βi) of beta-amyloid (aa 1-42) (available from American Peptide Co.) was intracerebroventricularly injected into each mouse according to the method described in Reference Example 1. For mice in a sham group, physiological saline, instead of the extract of Curcuma aromatica SALISB., was orally administered, and physiological saline, instead of beta-amyloid, was intracerebroventricularly injected. For mice in a control group, physiological saline, instead of the extract of Curcuma aromatica SALISB., was orally administered in the same manner as described above, and beta-amyloid was then intracerebroventricularly injected in the same manner as described above. On days 1 and 2 after the intracerebro ventricular injection, passive avoidance test was carried out according to the method described in Reference Example 2. The results are shown in FIG. 1, expressed with the average value of latencies for 10 mice. As seen from FIG. 1, while the mice in the control group showed a significant reduction in passive avoidance response time (PO.001) compared with those in the sham group, the mice of the test groups administered with 0.25 g/kg and 0.5 g/kg of the extract of Curcuma aromatica SALISB., respectively, showed a significant increase in passive avoidance response time (PO.05 for both groups). It was confirmed from these results that the extract of Curcuma aromatica SALISB. suppressed memory impairment due to accumulation of beta-amyloid.
Example 2: Prevention of senile dementia by Curcumin
40 ICR mice of 4-5 weeks old, weighing 20 to 25 g, were divided into 4 groups of each 10 mice. For mice in two test groups, Curcumin (available from Sigma Co.)
was dissolved in corn oil and then orally administered five times in amounts of 10 mg/kg and 100 mg/kg, respectively, at intervals of 10 hours. Here, the oral administration of Curcumin was conducted by using an oral syringe for mouse. Also, after administering Curcumin twice (19 hours after starting administration), 1.85 βg (5 l) of beta-amyloid (aa 1-42) was intracerebroventricularly injected into each mouse according to the method described in Reference Example 2. For mice in a sham group, corn oil, instead of Curcumin, was orally administered, and physiological saline, instead of beta-amyloid, was intracerebroventricularly injected. For mice in a control group, physiological saline, instead of Curcumin, was orally administered in the same manner as described above, and beta-amyloid was then intracerebroventricularly injected in the same manner as described above.
On days 1 and 2 after intracerebro ventricular injection, passive avoidance test was carried out according to the method describe in Reference Example 2. FIG. 2 shows the results of the test, expressed with an average value of latencies for 10 mice. Referring to FIG. 2, while the mice in the control group showed a significant reduction in passive avoidance response time (PO.001) compared with those in the sham group, the mice of the test groups administered with 10 g/kg and 100 g/kg of Curcumin, respectively, showed significant increases in passive avoidance response time (P<0.05 for mice administered with 10 mg/kg Curcumin and PO.01 for mice administered with 100 mg/kg Curcumin). The passive avoidance response time increased in a Curcumin-concentration dependent way. It was confirmed from these results that Curcumin suppressed memory impairment due to accumulation of beta-amyloid.
Test Example 1: Oral toxicity test for the extract of Curcuma aromatica SALISB.
Each 20 of female and male ICR mice of 4 weeks old, were bred at an animal room with conditions of 22+ 3 °C in temperature, 50+ 10% in relative humidity and 150-300 Lux in light intensity, for one week, and then divided into 4 groups each
having 5 female mice and 5 male mice.
For mice in four groups, the extract of Curcuma aromatica SALISB. prepared according to Preparation Example was dissolved in physiological saline and then orally administered once in amounts of 300, 1,000 and 3,000 mg/kg, respectively. For a period of 7 days after administration, a change in general symptoms and outbreak of dead animals were observed. 7 days after administration, the mice were killed and anatomized, following by examining their viscera with the naked eye. On and after administration, by measuring a change in body weight everyday, it was determined whether the animals showed a reduction in body weight due to the administered extract of Curcuma aromatica SALISB .
The result revealed no toxicity in any groups of mice administered with 3,000 mg/kg or less of the extract of Curcuma aromatica SALISB. Also, an autopsy of living animals resulted that no pathological symptoms were observed with the naked eye in any groups of mice administered with the extract of Curcuma aromatica SALISB. Further, for any mice of the groups, no reduction of body weight was observed.
Test Example 2: Oral toxicity test for Curcumin
By using Curcumin (available from Sigma Co.) dissolved in corn oil, an oral toxicity test for Curcumin was carry out in the same method as in Test Example 1.
The result revealed no toxicity in any groups of mice administered with 3,000 mg/kg or less of Curcumin. Also, an autopsy of living animals resulted that no pathological symptoms were observed in any groups of mice administered with
Curcumin with the naked eye. Further, for any mice of the groups, no reduction of body weight was observed.
Formulation Example: Hard gelatin capsule formulation
cellulose, 15 mg of isoflavone, 2.5 mg of Ginkgo biloba extract, 2 mg of extract of dried seed of Zizyphus spinosa, 0.25 mg of vitamin Bi, 0.3 mg of vitamin B2, 0.0025 mg of vitamin B3 and 2.5 mg of magnesium stearate were completely mixed, followed by filling into a hard gelatin capsule, thereby forming a hard gelatin capsule formulation.
Industrial Applicability
The composition according to the present invention, which comprises Curcumin or an extract of Curcuma aromatica SALISB. as an effective ingredient, can be advantageously used for preventing and treating senile dementia.
Claims
1. A pharmaceutical composition for preventing and treating senile dementia, comprising Curcumin or a pharmaceutically acceptable salt thereof as an effective ingredient.
2. A use of Curcumin or a pharmaceutically acceptable salt thereof in preparing a pharmaceutical composition for preventing and treating senile dementia.
3. A method for preventing and treating senile dementia by administering a therapeutically effective amount of Curcumin or a pharmaceutically acceptable salt thereof.
4. A pharmaceutical composition for preventing and treating senile dementia, comprising an extract of Curcuma aromatica SALISB. containing Curcumin, as an effective ingredient.
5. A use of an extract of Curcuma aromatica SALISB. containing Curcumin in preparing a pharmaceutical composition for preventing and treating senile dementia.
6. A pharmaceutical composition according to claim 4 or 5, wherein the extract of Curcuma aromatica SALISB. is extracted by a solvent selected from the group consisting of water, methanol, ethanol, acetone, chloroform, methylene chloride, and mixtures thereof.
7. A method for preventing and treating senile dementia by administering a therapeutically effective amount of an extract of Curcuma aromatica SALISB. containing Curcumin.
8. The method according to claim 7, wherein the extract of Curcuma aromatica SALISB. is extracted by a solvent selected from the group consisting of water, methanol, ethanol, acetone, chloroform, methylene chloride, and mixtures thereof.
9. A functional food for preventing senile dementia, comprising Curcumin as an effective ingredient.
10. A functional food for preventing senile dementia, comprising an extract of Curcuma aromatica SALISB. containing Curcumin, as an effective ingredient.
11. The functional food according to claim 10, wherein the extract of Curcuma aromatica SALISB. is extracted by a solvent selected from the group consisting of water, methanol, ethanol, acetone, chloroform, methylene chloride, and mixtures thereof.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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KR1020010013726A KR20020073847A (en) | 2001-03-16 | 2001-03-16 | Composition for preventing or treating dementia comprising curcumin or extract of curcuma aromatica |
KR2001/13726 | 2001-03-16 |
Publications (1)
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WO2002074295A1 true WO2002074295A1 (en) | 2002-09-26 |
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PCT/KR2002/000449 WO2002074295A1 (en) | 2001-03-16 | 2002-03-15 | A composition for the prophylaxis or treatment of senile dementia |
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WO (1) | WO2002074295A1 (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2003051380A2 (en) * | 2001-12-14 | 2003-06-26 | Council Of Scientific And Industrial Research | Compositions containeing curcuma extracts for the treatment of neurocerebrovascular disorders |
CN1312106C (en) * | 2003-03-28 | 2007-04-25 | 烟台同和医药科技有限公司 | Preparation method of water soluble curcumin composition salt |
WO2008048410A2 (en) * | 2006-09-19 | 2008-04-24 | Human Biomolecular Research Institute | Diagnostic methods and genetic markers for alzheimer disease |
WO2010106191A1 (en) * | 2009-03-20 | 2010-09-23 | Bioxtract S.A. | Pharmaceutical composition presenting anti-inflammatory properties |
US8895087B2 (en) * | 2005-05-30 | 2014-11-25 | Arjuna Natural Extracts, Ltd | Composition to enhance the bioavailability of curcumin |
US8993013B2 (en) * | 2005-05-30 | 2015-03-31 | Arjuna Natural Extracts, Ltd. | Composition to enhance the bioavailability of curcumin |
US9492402B2 (en) | 2005-05-30 | 2016-11-15 | Benny Antony | Formulation of curcuminoids with enhanced bioavailability of curcumin, demethoxycurcumin, bisdemethoxycurcumin and method of preparation and uses thereof |
US10159654B2 (en) | 2005-05-30 | 2018-12-25 | Arjuna Natural Extracts, Ltd | Formulation of curcumin with enhanced bioavailability of curcumin and method of preparation and treatment thereof |
US10286027B2 (en) | 2005-05-30 | 2019-05-14 | Arjuna Natural Extracts, Ltd. | Sustained release formulations of curcuminoids and method of preparation thereof |
US10543277B2 (en) | 2005-05-30 | 2020-01-28 | Arjuna Natural Private Limited | Formulation of curcumin with enhanced bioavailability of curcumin and method of preparation and treatment thereof |
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KR20020075122A (en) * | 2001-03-23 | 2002-10-04 | 권호정 | A method for extracting demethoxycurcumin from Curcuma aromatica, the demethoxycurcumin extracted by the method, the curcumin derivatives and functional drinks containing them |
KR100447668B1 (en) * | 2002-06-28 | 2004-09-08 | 현대약품공업주식회사 | Method for preparing functional drink comprising dispersing pieces of jelly containing water-insoluble bioactive materials |
KR100688907B1 (en) * | 2004-11-02 | 2007-03-02 | 한국화학연구원 | Composition comprising an extract of turmeric or curcuminoids for controlling rice blast |
KR102008774B1 (en) * | 2016-07-07 | 2019-08-09 | 우석대학교 산학협력단 | Composition for improvement of memory and cognition ability, prevention, delay, treatment or improvement of Alzheimer's disease, comprising extracts of Ecklonia stolonifera, Curcuma longa Rhizoma, Zingiber officinale Roscoe and red ginseng |
KR102046410B1 (en) * | 2017-06-26 | 2019-11-19 | 우석대학교 산학협력단 | Composition for improvement of memory and cognition ability, prevention, delay, treatment or improvement of Alzheimer's disease, comprising extracts of Curcuma longa Rhizoma, Chaenomeles sinensis Koehne fruit and Zingiber officinale Roscoe rhizome |
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US5861415A (en) * | 1996-07-12 | 1999-01-19 | Sami Chemicals & Extracts, Ltd. | Bioprotectant composition, method of use and extraction process of curcuminoids |
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WO2003051380A2 (en) * | 2001-12-14 | 2003-06-26 | Council Of Scientific And Industrial Research | Compositions containeing curcuma extracts for the treatment of neurocerebrovascular disorders |
WO2003051380A3 (en) * | 2001-12-14 | 2004-06-17 | Council Scient Ind Res | Compositions containeing curcuma extracts for the treatment of neurocerebrovascular disorders |
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US10543277B2 (en) | 2005-05-30 | 2020-01-28 | Arjuna Natural Private Limited | Formulation of curcumin with enhanced bioavailability of curcumin and method of preparation and treatment thereof |
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US9861677B2 (en) | 2005-05-30 | 2018-01-09 | Arjuna Natural Extracts, Ltd. | Composition to enhance the bioavailability of curcumin |
US10286027B2 (en) | 2005-05-30 | 2019-05-14 | Arjuna Natural Extracts, Ltd. | Sustained release formulations of curcuminoids and method of preparation thereof |
WO2008048410A3 (en) * | 2006-09-19 | 2008-10-23 | Human Biomolecular Res Inst | Diagnostic methods and genetic markers for alzheimer disease |
WO2008048410A2 (en) * | 2006-09-19 | 2008-04-24 | Human Biomolecular Research Institute | Diagnostic methods and genetic markers for alzheimer disease |
JP2010504332A (en) * | 2006-09-19 | 2010-02-12 | ヒューマン バイオモレキュラル リサーチ インスティテュート | Diagnostic method and genetic marker for Alzheimer's disease |
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WO2010106191A1 (en) * | 2009-03-20 | 2010-09-23 | Bioxtract S.A. | Pharmaceutical composition presenting anti-inflammatory properties |
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