CN104507486A - Pharmaceutical composition comprising mixed extract of zingiber officinale rosc, and paeonia lactiflora pallas for preventing or treating dementia and cognitive dysfunction - Google Patents
Pharmaceutical composition comprising mixed extract of zingiber officinale rosc, and paeonia lactiflora pallas for preventing or treating dementia and cognitive dysfunction Download PDFInfo
- Publication number
- CN104507486A CN104507486A CN201380039376.7A CN201380039376A CN104507486A CN 104507486 A CN104507486 A CN 104507486A CN 201380039376 A CN201380039376 A CN 201380039376A CN 104507486 A CN104507486 A CN 104507486A
- Authority
- CN
- China
- Prior art keywords
- rhizoma zingiberis
- radix paeoniae
- paeoniae alba
- mixed extract
- cognitive dysfunction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- 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)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
-
- 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)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The present invention relates to a pharmaceutical composition or a functional food composition comprising a mixed extract of Zingiber officinale ROSC and Paeonia lactiflora Pallas as an active ingredient for preventing or treating dementia and cognitive dysfunction.
Description
Technical field
The present invention relates to for dull-witted (dementia) and the prevention of cognitive dysfunction (cognitivedysfunction) or the pharmaceutical composition for the treatment of, more specifically, relate to a kind of comprise Rhizoma Zingiberis, the Radix Paeoniae Alba mixed extract as the prevention to dull-witted and cognitive dysfunction of active ingredient or treatment drug composition effective and functional health food.
Background technology
The whole world enters aging society rapidly, and therefore, the mankind pursue can without disease ground high quality of life of having good health and a long life.The prosperity of science causes life, thus along with aging population increase, the ratio as the dementia patients of neurodegenerative diseases increases.
Generally speaking, such as the alzheimer disease of Alzheimer (Alzheimer's Disease) is as the disease being feature with gradual cognitive afunction, quality of life is greatly reduced in individual or social, misfortune is caused to me and the people of periphery, after cancer, heart disease and apoplexy, become the fourth-largest reason of old man's death.
Although fall ill because of a variety of causes dull-witted, wherein the most convictive scientific reasons is as follows.The first, think that the concentration of the neurotransmitter (neurotransmitter) being called acetylcholine (acetylcholine) at cerebral hippocampus (hippocampus) position lowly has high association with dementia.With regard to dementia patients, the acetylcholinesterase (acetylcholine esterase) of the effect of choline (choline) is formed by means of performance makes acetylcholine hydrolyzation, acetylcholine is hydrolyzed, thus the relative concentration of acetylcholine is low.Therefore have report to think, when acetylcholine esterase inhibition, the concentration of the acetylcholine of brain rises, and the symptom of dementia patients improves.As acetylcholinesteraseinhibitors inhibitors, obtain FDA approval and medicine as dementia treatment agent application has donepezil (donepezil), galantamine (galanthamine), Rivastigmine (rivastigmine) etc.
But this acetylcholinesterase inhibitor thing major part has the Cholinergic side effect of peripheral nerve, and the half-life is too short, there are the serious side effects such as liver toxicity (Br.J.Psychiatry, 138,46,1981).
The second, amyloid-beta (Amyloid beta; A β) coagulation of speckle and the caking of iuntercellular nerve fiber be considered to the main cause of bringing out Alzheimer dementia, and this finds in a large number in the brain of dementia patients.Amyloid-beta (A β) is from amyloid-beta precursor protein (β-amyloidprecursor protein; β APP) generated by the transmission effect by means of BACE1 (β-site APP-cleavingenzyme 1) and beta-secretase (β-secretase) activity.The process LAN of BACE1 makes the beta-secretase transmission of APP increase, and generates amyloid-beta.The amyloid-beta of generation like this suppresses signal transmission between neurocyte, brings out inflammation.Therefore have report to think, when suppressing the coagulation of amyloid-beta, the damage of cranial nerve reduces, and cognitive function takes a turn for the better.
Cognitive dysfunction shows attention reduction, learning capacity reduction, hypomnesis, sensation cognitive function (perception) obstacle etc.Memory disorder is as common sympton, and major part is complete to the memory of past event, but obstacle appears in the function of mnemonic learning fresh information, encounters difficulties in the study.
Recently, being intended to utilize can acetylcholine esterase inhibition or suppress to bring out the medicinal substances extract of the coagulation of the amyloid-beta of protein as dementia and the research that prevents or treat dementia or cognitive dysfunction is active carries out (No. 10-2005-0095819th, Korean Patent Publication No. etc.).The side effect of medicinal substances extract is far smaller than other medicines, but according to circumstances, may also have other side effect, and its therapeutic effect is still insufficient so far.
Summary of the invention
The present invention has the medical material of effect to improvement dementia and cognitive dysfunction in order to find, utilization comprises Rhizoma Zingiberis, 46 kinds of medical materials of the Radix Paeoniae Alba develop a kind of mixed extract, it has obstruction acetylcholinesterase, the activity suppressing amyloid-beta coagulation and inducing neural somatomedin (nervegrowth factor, the effect of NGF) secreting, at (the novel object recognition test of the recognition tests to new things of the memory injury animal model of inducing with scopolamine (scopolamine); NORT), passive avoidance test (passive avoidance test; PAT), in Y type labyrinth test (Ymaze test), there is Improving memory power effect, and have and make study enhancement and spatial perception ability bring up to superior efficacy close to intact animal's group, by confirming to utilize its effect, thus complete the present invention.
The object of this invention is to provide a kind of comprise therapeutics effective dose Rhizoma Zingiberis, the dementia of acceptable carrier and cognitive dysfunction prevention or medicine for treatment compositions on Radix Paeoniae Alba mixed extract and pharmaceutics.
The object of the invention is also to provide a kind of Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract of comprising as the dementia of active ingredient and cognitive dysfunction improvement functional food composite.
In order to reach object described above, the invention provides a kind of dull-witted and cognitive dysfunction prevention or medicine for treatment compositions, wherein, comprising acceptable carrier on the Rhizoma Zingiberis of therapeutics effective dose, Radix Paeoniae Alba mixed extract and pharmaceutics.
The present invention also provides a kind of dull-witted and cognitive dysfunction improvement functional food composite, wherein, comprises Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract as active ingredient.
The invention provides and prevent and/or treat powerful active ingredient as to dull-witted and cognitive dysfunction and comprise the pharmaceutical composition of Rhizoma Zingiberis of the present invention, Radix Paeoniae Alba mixed extract.Rhizoma Zingiberis, the Radix Paeoniae Alba mixed extract of comprising of the present invention, as the pharmaceutical composition of active ingredient and/or food compositions, can prevent and/or treat dementia, and prevention or treatment memory disorder, in addition, can also promote study or memory.
Accompanying drawing explanation
Fig. 1 represents neuroglial cytoma (glioma) the C6 cell strain for Mus, and the nerve growth factor (nerve growth factor, NGF) of Rhizoma Zingiberis of the present invention, Radix Paeoniae Alba mixed extract secretes the chart of inducing effect.
Fig. 2 represents neuroglial cytoma (glioma) the C6 cell strain for Mus, and the NGF of the different blending ratios of Rhizoma Zingiberis of the present invention, Radix Paeoniae Alba mixed extract secretes the chart of facilitation effect and Cytotoxic evaluation.
Fig. 3 be represent Rhizoma Zingiberis of the present invention, Radix Paeoniae Alba mixed extract different blending ratios in BV-2 cell with LPS induction the secretion inhibition of NO and the chart of Cytotoxic evaluation.
Fig. 4 represents the Mus for inducing with scopolamine, and each match ratio of Rhizoma Zingiberis of the present invention, Radix Paeoniae Alba mixed extract is at recognition tests (the novel object recognition test to new things; NORT) memory in improves the chart of effect.Cognitive index (recognition index) is the ratio exploring new object required time.
Fig. 5 represents the Mus for inducing with scopolamine, and Rhizoma Zingiberis of the present invention, the memory of Radix Paeoniae Alba mixed extract in Y type labyrinth test (Y maze test) improve the chart of effect.
Fig. 6 represents the Mus for inducing with scopolamine, and Rhizoma Zingiberis of the present invention, Radix Paeoniae Alba mixed extract are at passive avoidance test (passive avoidance test; PAT) memory in improves the chart of effect.
Detailed description of the invention
The invention provides dementia and cognitive dysfunction prevention or medicine for treatment compositions, wherein, comprise acceptable carrier on the Rhizoma Zingiberis of therapeutics effective dose, Radix Paeoniae Alba mixed extract and pharmaceutics.
Alzheimer and vascular dementia (vascular dementia), parkinson disease, mild cognitive impairment (mild cognitiveimpairment), alzheimer disease, Frontotemporal dementia etc. can be comprised in dementia of the present invention and cognitive dysfunction.
The Rhizoma Zingiberis used in the present invention and the Radix Paeoniae Alba were used as disease treatment and prevention object in the past always as South Korea's medical material.
Rhizoma Zingiberis (dried rhizomes of Zingiber officinale roscoe) carries out drying to the rhizome of the perennial herb Rhizoma Zingiberis Recens belonging to Rhizoma Zingiberis Recens section and obtains, Rhizoma Zingiberis Recens be just widely used as since ancient times strong (
), strong essence (
), anticancer food.Rhizoma Zingiberis Recens or there is as the gingerol etc. of the pungent composition of Rhizoma Zingiberis Recens the effect of coagulation hindering acetylcholinesterase or suppress amyloid-beta, thus treatment also powerful (Kim DS et al., the J AlternComplement Med.2007Apr to Alzheimer etc. is considered to; 13 (3): 333-40).
The Radix Paeoniae Alba (Paeonia lactiflora Pallas) for belonging to the herbaceos perennial of Ranunculaceae, containing do dimension glycocide peoniflorin (paeoniflorin) and as alkaloidal paeonine (paeonine), tannin, resin and benzoic acid etc.The Radix Paeoniae Alba is known has neuroprotective and antioxidant activity (No. 10-2006-0023885th, Korean Patent Publication No. etc.).
The invention is characterized in, the mixed extract containing Rhizoma Zingiberis, the Radix Paeoniae Alba, as active ingredient, is further characterized in that, uses the mixed extract of Rhizoma Zingiberis and the Radix Paeoniae Alba, thus compared with when Rhizoma Zingiberis, the Radix Paeoniae Alba individually being used as extract, cumulative effects increases.In addition, when using by specific match ratio, its effect maximizes further.
The each medical material composition used in the present invention is for benchmark with the weight of drying.
The mixed extract of described Rhizoma Zingiberis, the Radix Paeoniae Alba can be mixed extract Rhizoma Zingiberis, the Radix Paeoniae Alba mixed by the ratio of 1:10-10:1, is preferably the mixed extract mixed by the ratio that Rhizoma Zingiberis, the Radix Paeoniae Alba press 1:5-5:1.Specify that toxicity is minimum, and side effect is minimum, demonstrates optimal efficacy in composition formation as above with within the scope of content ratio.
Described Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract can carry out the abstraction process that comprises the following steps and obtain, and described step is: by Rhizoma Zingiberis, the Radix Paeoniae Alba to be selected from C
1~ C
4alcohol, normal hexane, ethyl acetate, n-butyl alcohol, Extraction solvent in chloroform and their mixed solvent extract.More preferably, described Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract can be with ethanol extraction Rhizoma Zingiberis, the Radix Paeoniae Alba and the ethanol extraction obtained.
The use amount of described Extraction solvent does not have large restriction, such as, relative to powder test portion 1 weight of Rhizoma Zingiberis, the Radix Paeoniae Alba, can use, preferably, can use by the ratio of about 5 to 10 times of volumes by about 1 to 10 times of volume.In addition, described extraction can be little of 24 hours periods about 1, preferably, can be little of 5 hours periods about 1, undertaken by extracting method such as merceration extraction, hot water extraction, ultrasonic extraction, reflux cooling extractions.Preferably, described extraction can be carried out according to 79 DEG C of reflux cooling extraction methods, and in addition, described leaching process can carry out by single or multiple, preferably, can repeatedly carry out about about 3 times.The extracting solution obtained can utilize usual way as required, such as, at about 20 to 100 DEG C, and preferably concentrating under reduced pressure or drying under reduced pressure at about 30 to 70 DEG C, thus obtain Rhizoma Zingiberis Recens extract with liquid or powder morphology.
Described Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract, in order to improve the content of active ingredient, can carry out the abstraction process that adds and obtain.That is, the high Rhizoma Zingiberis of effective component content, Radix Paeoniae Alba mixed extract can be obtained by also carrying out the abstraction process that comprises the following steps: (a) is with C
1~ C
4alcohol extraction Rhizoma Zingiberis, the Radix Paeoniae Alba step; And (b) adds water in described (a) middle extract obtained and normal hexane extracts, to the step that the normal hexane layer obtained is separated.
In addition, optionally, can by the abstraction process that carries out comprising the following steps (and as required the chromatographic isolation operation added): (a) is with C
1~ C
4alcohol extraction Rhizoma Zingiberis, the Radix Paeoniae Alba step; (b') water is added in the extract obtained described step (a) and normal hexane extracts, to the step that the water layer obtained is separated; And add ethyl acetate in (c) water layer of obtaining in described step (b') and extract, to the step that the ethyl acetate layer obtained is separated; Or by the abstraction process that carries out comprising the following steps (and as required the chromatographic isolation operation added): (a) is with C
1~ C
4alcohol extraction Rhizoma Zingiberis, the Radix Paeoniae Alba step; (b') water is added in the extract obtained described step (a) and normal hexane extracts, to the step that the water layer obtained is separated; (c') add ethyl acetate in the water layer obtained in described step (b') to extract, to the step that the water layer obtained is separated; And add n-butyl alcohol in (d) water layer of obtaining in described step (c') and extract, to the step that the n-butanol layer obtained or water layer are separated, thus obtain the high Rhizoma Zingiberis of effective component content, Radix Paeoniae Alba mixed extract.
" the therapeutics effective dose " that use in the present invention means common prevention, reduction or alleviates the amount required at least one disease symptoms in the disease recorded in such as the application for the treatment of.
Compositions of the present invention comprises described extract 0.01-95 % by weight relative to composition total weight.
The compositions comprising extract of the present invention can comprise pharmaceutically acceptable carrier and preparation becomes various form, the form of compositions for oral dosage form, external preparation, suppository and the sterilizing injecting solutions such as such as powder, granule, tablet, capsule, suspension, Emulsion, syrup, aerosol.Particularly preferably, compositions for oral dosage form can be become by preparation.
On described pharmaceutics, acceptable carrier comprises lactose, dextrose, sucrose, pear oligose alcohol, mannitol, xylitol, erythritol, maltose alcohol, starch, Radix Acaciae senegalis, alginate, gelatin, calcium phosphate, calcium silicates, cellulose, methylcellulose, microcrystalline Cellulose, polyvinylpyrrolidone, water, methylhydroxy benzoic ether, nipasol, Talcum, magnesium stearate and mineral wet goods.In addition, diluent or the excipient such as filler, extender, bonding agent, wetting agent, disintegrating agent, surfactant is comprised.Solid preparation for oral administration comprises tablet, pill, powder, granule, capsule etc., this solid preparation can comprise the excipient of more than at least one, such as starch, calcium carbonate (calcium carbonate), sucrose (sucrose) or lactose (lactose), gelatin etc., can comprise the lubricant etc. of magnesium stearate, Talcum and so on.Liquid formulation for oral use comprises suspending agent, interior liquor, Emulsion, syrup etc., can comprise the diluent such as water, liquid Paraffin, wetting agent, sweeting agent, aromatic, preservative agent etc.Parenteral preparation comprises aqueous solution, non-aqueous solvent, suspending agent, Emulsion, lyophilized formulations, the suppository of sterilizing, as non-aqueous solvent, suspending agent, comprise the injectable esters etc. of propylene glycol (propylene glycol), the plant oil of Polyethylene Glycol, such as olive oil, such as ethyl oleate.As the base of suppository, semi-synthetic fatty acid ester (witepsol), Polyethylene Glycol, tween (tween) 61, cocoa ester, laurate, glycerin gelatine etc. can be used.
The dosage of pharmaceutical composition comprising Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract of the present invention, different from the degree of the state of patient and body weight, disease, drug form, route of administration and period, but suitably can be selected by those skilled in the art.Such as, 1 day can administration 0.01 to 500mg/kg, preferably, and can the consumption of administration 10 to 300mg/kg, described administration also can once a day or administration several times.
The present invention goes back providing package containing Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract as the learning disorder of active ingredient or the improvement of memory disorder or anesis food compositions.
In described food compositions, Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract can contents according to the above description and obtaining.
Food compositions of the present invention can be used as healthy functions food.Above-mentioned what is called " healthy functions food ", mean and use there is useful functional raw material or composition to human body of No. 6727th, healthy functions food relevant law regulation and the food that manufactures and process, so-called " functional ", mean the structure for human body and function, absorb to obtain for the purpose of adjustment nutrient or the effect useful to the health purpose of such as physiological role etc.
Food compositions of the present invention can comprise common food additives, for whether being suitable as described " food additives ", as long as no other regulation, according to the general provisions of the public allusion quotation of food additives of food and drug safety Room approval and conventional test method etc., judge according to about the rule of corresponding kind and benchmark.
As the kind of including in described " the public allusion quotation of food additives ", such as, the mix preparation class such as the natural additives such as the syntheticses such as ketone, glycine, potassium citrate, nicotinic acid, cinnamic acid, Fructus Kaki pigment, Radix Glycyrrhizae extract, microcrystalline Cellulose, kaoliang color, guar gum, Pidolidone preparation of sodium, Noodles interpolation alkaline agent, antiseptic, tar colorant preparation can be enumerated.
Food compositions of the present invention for the object improving learning disorder or memory disorder or mitigation symptom, or for promoting the object of study or memory, can manufacture and be processed into the form of tablet, capsule, powder, granule, liquid state, ball etc.
Food compositions of the present invention, relative to composition total weight, can comprise Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract 0.01 to 95 % by weight, preferably, can comprise 1 to 80 % by weight.
Such as, after the mixture of Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract and excipient, bonding agent, disintegrating agent and other additive can be made granule with usual way by the healthy functions food of described tablet form, add lubricant etc. and carry out compression forming, or to the direct compression forming of described mixture.In addition, the healthy functions food of described tablet form can as required containing correctives etc., can also as required with suitable coating agent (
) be coated to.
In the healthy functions food of capsule form, hard rubber wafer can be filled the mixture of the additives such as Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract and excipient or its shot-like particle or coating shot-like particle and be manufactured in common hard capsules, and the mixture of the additives such as Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract and excipient can be filled in the capsule bases such as gelatin and manufacture by soft capsules.Described soft capsules can contain the plasticizer such as glycerol or sorbitol, coloring agent, preservative agent etc. as required.
The healthy functions food of ball form can carry out molding to the mixture of Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract and excipient, bonding agent, disintegrating agent etc. and manufacture in a suitable approach, can be coated to white sugar or other suitable coating agent as required, or be coated to obducens with starch, Talcum or suitable material.
The mixture of described Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract, excipient, bonding agent, disintegrating agent etc. can manufacture granular with proper method by the healthy functions food of particle shape, can contain flavouring agent, correctives etc. as required.
Term definition for the described excipient, bonding agent, disintegrating agent, lubricant, correctives, flavouring agent etc. of the present application is recorded in document known in this field, its function etc. comprises identical and even similar content, and (great Han pharmacopeia explains orally a section, Wen Xingshe, pharmacy university of Korea S consultation, 5th revised edition, p33-48,1989).
Below by embodiment and test example, illustrate in greater detail the present invention.But these embodiments and test example are used for carrying out example to the present invention, and scope of the present invention is not defined in these embodiments and test example.
< embodiment >
Embodiment 1: the manufacture of Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract
Grinding Rhizoma Zingiberis 0.5kg, Radix Paeoniae Alba 1.5kg, add 95% ethanol of 20 liters, and at 79 DEG C, reflux cooling extracts after 3 hours and filters, separating filtrate.The filtrate of acquisition be all combined, carry out concentrating under reduced pressure, after removing solvent, remove moisture completely by lyophilizing, acquisition Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract are about 340g.
In addition, in order to confirm the optimum efficiency of each match ratio, extracting by match ratio as shown in table 1 below, having manufactured the extract of each match ratio.
Table 1
[table 1]
The secretion effect of test example 1. nerve growth factor (NGF) confirms
Make use of neuroglial cytoma (glioma) the C6 cell strain of the Mus of known secretory nerve somatomedin (nerve growth factor, NGF).C6 cell is bought from Korea Cell strain bank and is used (KCLB No.10107).C6 cell uses the sodium bicarbonate (NaHCO supplementing 3.4g/L
3, sodium bicarbonate), the DMEM culture medium (Gibco BRL, the U.S.) of 10% hyclone (fetal bovine serum) and Pen .-Strep antibiotic (10000U/ml) 1% cultivates.
The RPMI1640 culture medium (Gibco BRL, the U.S.) supplementing 2.0g/L sodium bicarbonate, 10% horse serum (horse serum), 5% hyclone and Pen .-Strep antibiotic (10000U/ml) 1% is used to cultivate for the PC12 cell understood based on the Neural Differentiation of NGF.The hyclone used and horse serum before use, make it deactivation and use after 30 minutes at 55 DEG C, supplies in the cell culture incubator of the carbon dioxide of 5% cultivate in the humidity of maintenance 70% and the temperature of 37 DEG C.
Carry out 0.25% trypsin Trypsin)-EDTA (Gibco BRL, the U.S.) process, after making to be attached to the C6 cell detachment of 100mm culture vessel, add 10ml fresh culture and after making cell suspending liquid, utilize cell number measuring instrument to measure and calculate the cell number of living.Based on the value calculated, to comprise 2 × 10 in 100mm culture dish
6the mode of individual cell carries out plant division.Cultivate after 24 hours, remove original culture medium, be replaced by embodiment 1 is obtained Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract respectively by 10,50,100 μ g/ml concentration add 2% hyclone DMEM culture medium 10ml, after again cultivating 24 hours, obtain culture medium respectively.By obtain culture medium at 1500 rpm centrifugalize after 10 minutes, again only collect upper liquid.
The measurement of the nerve growth factor of C6 emiocytosis is measured treatment conditions culture medium in test kit (DY556, R & D system, the U.S.) at nerve growth factor and carries out quantitatively.In order to understand Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract induces on nerve growth factor secretion the impact brought, and cultivates in C6 cell after process, and quantitative analysis nerve growth factor in the conditioned medium obtained, its result as shown in Figure 1.
In order to understand cytotoxicity, collect the upper liquid of cultivating in above-described embodiment, in remaining cell, with 3-[4,5-dimethylthiazole-2-base]-2,5-diphenyltetrazolium bromide bromine salt (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) (MTT, sigma Cat#M5655) process 1 hours after, add DMSO 200 μ l, after making cytolysis, measure with the ELISA microplate reader of 570nm wavelength value, evaluate and have no cytotoxicity.
As negative control group, when non-processor group is calculated by 100% basis conversion, confirm the ratio according to the Radix Paeoniae Alba, Rhizoma Zingiberis mixed extract, occur that different NGF secretes facilitation effect, detected by MTT that to confirm this be not demonstrating the facilitation effect in Cytotoxic scope.In several cases, best matching requirements is judged as with the Radix Paeoniae Alba 3: during the ratio mixed extraction of Rhizoma Zingiberis 1, to secrete facilitation effect the highest for NGF.
Test example 2: the NO about neuroinflamation secretes inhibition and confirms
BV-2 cell as mice source Glial cells is cultivated in the DMEM culture fluid containing 5% hyclone (fetalbovine serum) and 1% penicillin (penicillin)/streptomycin (streptomycin).
Described BV-2 cell is pressed 3>10 in the 96 each holes of orifice plate
4after individual number plant division, cultivate 24 hours.Then, the Rhizoma Zingiberis manufactured in embodiment 1, Radix Paeoniae Alba mixed extract are processed by concentration, after 30 minutes, by liopopolysaccharides (lipopolysaccharide; LPS) with concentration 100ng/ml process, cultivate 24 hours.After 24 hours, after collecting upper liquid, in dative, this (Griess) reagent (N-(1-naphtyl) ethylenediamine dihydrochloride (sigma cat#N9125)+Sulfanilic acid in 5%phosphoric acid (sigma cat#S9251)) mixes by 1:1, after reacting 10 minutes at normal temperatures, utilize ELISA microplate reader (ELISA plate reader), in 570nm wavelength value, measure absorbance.After having collected upper liquid in remaining cell, with 3-[4,5-dimethylthiazole-2-base]-2,5-diphenyltetrazolium bromide bromine salt (MTT, sigma Cat#M5655) process 1 hours after, add DMSO 200 μ l, after making cytolysis, utilize the ELISA microplate reader of 570nm wavelength value to measure, evaluate and have no cytotoxicity.Analyze Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract on inflammation be correlated with NO secretion impact, its result is as shown in Figure 3.
As negative control group, when the group processing LPS is calculated by 100% basis conversion, confirm the ratio according to the Radix Paeoniae Alba, Rhizoma Zingiberis mixed extract, occur that different NO secretes inhibition, detected by MTT that to confirm this be secrete inhibition not demonstrating the NO in Cytotoxic scope.In several cases, best matching requirements is judged as the Radix Paeoniae Alba 3: the ratio of Rhizoma Zingiberis 1 and the Radix Paeoniae Alba 1: the mixed extraction of Rhizoma Zingiberis 1, and NO secretion inhibition is high.
Test example 3: with (the novelobject recognition test of the recognition tests to new things in the animal model of scopolamine induction; NORT)
In order to the cognitive competence and memory that confirm Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract in the memory impairment animal model utilizing scopolamine to induce promote effect, with following implementation Process.
Buy ICR system male mice in 7 week age (30-35g) from Ao Li favourite biotech firm (Orient Bio), raise at the animal feeding room of pharmacy institute of Kyung Hee University and within more than 1 week, make it to adapt to, used.Water and feedstuff freely absorb, and temperature (22 ± 2 DEG C), humidity (53 ± 3%) and light and shade cycle (12 hours) regulate automatically.
Mus is divided into 9 groups, often organizes 8.After adapting to 1 week, 1st group (matched group) is 5mL mono-day by 0.5% methylcellulose (methyl cellulose) by the every kg body weight of mice, oral administration 1 time on the 1st, 2nd group (individually dosed group of scopolamine), 3rd group (donepezil 1mg/kg administration group), 4th group (Rhizoma Zingiberis extract 50mg/kg administration group), 5th group (Radix Paeoniae Alba extract 50mg/kg administration group), 6th group (Rhizoma Zingiberis 3: the Radix Paeoniae Alba 1 ratio mixed extract 50mg/kg administration group), 7th group (Rhizoma Zingiberis 1: the Radix Paeoniae Alba 1 ratio mixed extract 50mg/kg administration group), 8th group (Rhizoma Zingiberis 1: the Radix Paeoniae Alba 3 ratio mixed extract 50mg/kg administration group) is the oral administration of drugs that will be dissolved in 0.5% methylcellulose (methyl cellulose) during a day, 1 day 1 time.
Once, administration is after 30 minutes, and intraperitoneal administration scopolamine (1mg/kg), implemented NORT after 30 minutes for oral administration of drugs.Animal is moved on to action observation ward by NORT, adapts to after 5 minutes, in the exposure test of 3 minutes, press 30cm interval placement same object 2 (1set) in chest after, measures animal explored object time 3 minutes periods.After one day, in extraction test, 1, the object provided when preparing original exposure in identical chest and 1, the object newly replaced, measure the time that animal is explored.Its result as shown in Figure 4.
Test example 4: with Y-labyrinth test (Y maze test) in the animal model of scopolamine induction
Mus is divided into 4 groups, often organizes 10.Make it adaptation after 1 week, 1st group (matched group) is 5mL mono-day by 0.5% methylcellulose (methyl cellulose) by the every kg body weight of mice, oral administration 1 time on the 1st, 2nd group (individually dosed group of scopolamine), the 3rd group (Radix Paeoniae Alba, Rhizoma Zingiberis mixed extract 50mg/kg), the 4th group (donepezil 1mg/kg administration group) are the oral administration of drugs that will be dissolved in 0.5% methylcellulose (methyl cellulose) during a day, 1 day 1 time.
Once, administration is after 60 minutes, and intraperitoneal administration scopolamine (1mg/kg), implements Y labyrinth after 30 minutes for oral administration of drugs.
Y labyrinth (Y maze) device is made up of identical 3 arms (arm) (horizontal 8cm, longitudinal 30cm, high 14cm), mutually respectively by the first retainer configuration of 120 °.After making mice be positioned at side arm end, it is made freely to walk about in Y labyrinth 8 minutes periods.Measure the number of times and order that enter each arm, evaluate spontaneous change (spontaneous alteration) (%).Changing (alteration) when entering 3 arm (arm) successively, being defined as ABC, BCA, CAB etc.% changes (alteration) and calculates with following mathematical expression 1.
[mathematical expression 1]
% change=[always changing number]/[total degree-2 of arm entry (arm)] × 100
Described Y maze test result, does not carry out the matched group of the administration of scopolamine, and demonstrate the change (spontaneous alteration) of 65%, the mice of an intraperitoneal administration scopolamine, Impairment of Memory, its numerical value is reduced to 47%.On the other hand, by the mice of 50mg/kg/day oral administration Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract, spontaneous change (spontaneous alteration) is significantly increased to 58%, can confirm that memory improves.Its result as shown in Figure 5.
Test example 5: with passive avoidance test (passiveavoidance test) in the animal model of scopolamine induction
Mice is divided into and often organizes 10.1st group (matched group) is 5mL by 0.5% methylcellulose (methyl cellulose) by the every kg body weight of mice, oral administration 3 days, 2nd group is donepezil (Donepezil) the 1mg/kg administration group being dissolved in 0.5% methylcellulose, and the 3rd group is just will be dissolved in the Rhizoma Zingiberis of 0.5% methylcellulose, Radix Paeoniae Alba mixed extract by 50mg/kg oral administration 3 days.By 1 day 1 time oral administration 3 days, last oral administration, after 1 hour, carried out passive avoidance test (passive avoidance task) as follows.
Passive avoidance test is divided in the assay device of two same space in internal structure, first day is between door is placed in by central authorities, turn on light in side, under the state of opposite side dark, make laboratory animal after 10 seconds were first stayed in bright side, door between opening, when it enters dark space, give the electricity irritation of 0.25mA to vola.After 24 hours, carry out passive avoidance test in the same way, now, measure the time of staying at bright place.Its result as shown in Figure 6.
Matched group demonstrates 150 ± 3.39 seconds, keep because of the memory caused that shocks by electricity, donepezil administration group is about 90 seconds, Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract 50mg/kg administration group are about 120 seconds, scopolamine administration group is 40 seconds, significantly, Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract administration group significantly increase the holdup time (p<0.05).
Claims (8)
1. dementia and cognitive dysfunction prevent or a medicine for treatment compositions, it is characterized in that, comprise acceptable carrier on Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract and pharmaceutics.
2. dementia according to claim 1 and cognitive dysfunction prevention or medicine for treatment compositions, it is characterized in that, described Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract are Rhizoma Zingiberis and the Radix Paeoniae Alba ratio mixed extraction by 1:10 to 10:1.
3. dementia according to claim 1 and cognitive dysfunction prevent or medicine for treatment compositions, it is characterized in that, described Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract carry out abstraction process and obtain, and described abstraction process comprises Rhizoma Zingiberis, Radix Paeoniae Alba mixture to be selected from C
1-C
4alcohol, normal hexane, ethyl acetate, n-butyl alcohol, Extraction solvent in chloroform and their mixed solvent carry out the step extracted.
4. dementia according to claim 1 and cognitive dysfunction prevention or medicine for treatment compositions, it is characterized in that, described Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract are with ethanol extraction Rhizoma Zingiberis, Radix Paeoniae Alba mixture and obtaining.
5. dementia according to claim 1 and cognitive dysfunction prevent or medicine for treatment compositions, and it is characterized in that, described Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract comprise 0.01-95 % by weight relative to composition total weight.
6. dementia according to claim 1 and cognitive dysfunction prevent or medicine for treatment compositions, it is characterized in that, the dosage form of described pharmaceutical composition is be selected from the compositions for oral dosage form in powder, granule, tablet, capsule, suspension, Emulsion and syrup.
7. a food compositions, is characterized in that, comprises acceptable additive in pharmaceutical composition according to claim 1 and bromatology.
8. food compositions according to claim 7, is characterized in that, described food compositions comprises Rhizoma Zingiberis, Radix Paeoniae Alba mixed extract 0.01 to 95 % by weight relative to composition total weight.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2012-0086161 | 2012-08-07 | ||
| KR20120086161A KR101492688B1 (en) | 2012-08-07 | 2012-08-07 | Pharmaceutical composition comprising mixed extracts of paeonia lactiflora pallas and dried rhizomes of zingiber officinale roscoe for preventing or treating of dementia and cognitive dysfunction |
| PCT/KR2013/007118 WO2014025202A1 (en) | 2012-08-07 | 2013-08-07 | Pharmaceutical composition comprising mixed extract of zingiber officinale rosc, and paeonia lactiflora pallas for preventing or treating dementia and cognitive dysfunction |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104507486A true CN104507486A (en) | 2015-04-08 |
Family
ID=50068367
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380039376.7A Pending CN104507486A (en) | 2012-08-07 | 2013-08-07 | Pharmaceutical composition comprising mixed extract of zingiber officinale rosc, and paeonia lactiflora pallas for preventing or treating dementia and cognitive dysfunction |
Country Status (3)
| Country | Link |
|---|---|
| KR (1) | KR101492688B1 (en) |
| CN (1) | CN104507486A (en) |
| WO (1) | WO2014025202A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412901A (en) * | 2016-01-22 | 2016-03-23 | 王丹旎 | Traditional Chinese medicine composition for treating Parkinson's disease as well as preparation method and application of traditional Chinese medicine preparation |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160103729A (en) | 2015-02-25 | 2016-09-02 | 충남대학교산학협력단 | Composition for prevention and treatment of cognitive disorder comprising extracts of Mulberry |
| KR101634619B1 (en) | 2016-03-14 | 2016-06-29 | 주식회사 그린메디넷 | Dementia cognition evaluating device and apparatus performing the same |
| KR102248093B1 (en) | 2019-10-11 | 2021-05-04 | 제천한약영농조합법인 | Manufacturing method of Liquor using Gastrodia Elata, Red Ginsing and Angelica gigas Nakai |
| CN115844958A (en) * | 2021-09-24 | 2023-03-28 | 宁波立华制药有限公司 | Preparation method of total glucosides of paeony |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060023884A (en) * | 2004-09-11 | 2006-03-15 | 정우약품공업 주식회사 | Composition comprising the extract of paeoniae radix having anti-oxidative activity |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20040053715A (en) * | 2002-12-13 | 2004-06-24 | (주)바이오랩 | Inhibition activity of job's tears extract against sucrase, maltase and glucoamylase and compositions containing job's tears extract for regulation of blood sugar |
| KR100700065B1 (en) * | 2004-04-20 | 2007-03-27 | 신준식 | A composition of chinese drugs having neuro-protecting activity |
| KR20110089223A (en) * | 2010-01-30 | 2011-08-05 | 원광대학교산학협력단 | A composition comprising the standardized fraction of ginger extract containing 6-gingerol as a standard for the preventing and treating of neuro-degenerative diseases |
-
2012
- 2012-08-07 KR KR20120086161A patent/KR101492688B1/en active IP Right Grant
-
2013
- 2013-08-07 WO PCT/KR2013/007118 patent/WO2014025202A1/en active Application Filing
- 2013-08-07 CN CN201380039376.7A patent/CN104507486A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060023884A (en) * | 2004-09-11 | 2006-03-15 | 정우약품공업 주식회사 | Composition comprising the extract of paeoniae radix having anti-oxidative activity |
Non-Patent Citations (5)
| Title |
|---|
| GIL-SAENG JEONG等: "Neuroprotective Effects of the Extract of Zingiberis Rhizoma", 《KOR. J. PHARMACOGN.》 * |
| MUHAMMAD N. GHAYUR等: "Muscarinic, Ca++ antagonist and specific butyrylch olinesterase inhibitory activity of dried ginger extract might explain its use in dementia", 《JOURNAL OF PHARMACY AND PHARMACOLOGY》 * |
| 刘昆: "《单方活用巧用图文百科》", 31 December 2011, 河北科学技术出版社 * |
| 刘步平: "《中华药酒治病养生全书》", 31 March 2009, 化学工业出版社 * |
| 明亮等: "白芍总甙对小鼠学习记忆行为的影响", 《安徽医科大学学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412901A (en) * | 2016-01-22 | 2016-03-23 | 王丹旎 | Traditional Chinese medicine composition for treating Parkinson's disease as well as preparation method and application of traditional Chinese medicine preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| KR101492688B1 (en) | 2015-02-12 |
| WO2014025202A8 (en) | 2015-02-12 |
| KR20140019967A (en) | 2014-02-18 |
| WO2014025202A1 (en) | 2014-02-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112274620B (en) | Traditional Chinese medicine composition for treating novel coronavirus pneumonia, preparation method, detection method and application thereof | |
| CN1322821C (en) | Natto powder and preparing method and health food containing such natto powder | |
| CN104507486A (en) | Pharmaceutical composition comprising mixed extract of zingiber officinale rosc, and paeonia lactiflora pallas for preventing or treating dementia and cognitive dysfunction | |
| CN104784618A (en) | Traditional Chinese medicine composition for treating headache | |
| CN101455690A (en) | Traditional Chinese medicine composition for treating infantile indigestion with food retention and preparation method and quality control method thereof | |
| WO2010054520A1 (en) | Pharmaceutical composition for purifing vein and preparation method thereof | |
| KR20140105411A (en) | A Chinese medicine composition and its preparation method and drug application in the treatment of hyperlipidemia | |
| CN101884703A (en) | Application of medicinal composition in preparation of autoimmune disease treatment medicaments | |
| CN106822739A (en) | A kind of integration of drinking and medicinal herbs prevents and treats the particle of senile dementia | |
| KR20090071704A (en) | Composition for prevention and treatment of the dementia | |
| CN102895387B (en) | Kidney-yang-warming medicine composition, and preparation thereof and preparation method thereof | |
| CN102805836B (en) | A kind of Chinese medicine composition for the treatment of primary hepatocarcinoma and preparation method thereof | |
| KR101580267B1 (en) | Composition for improving attention and concentration and method of preparing the extracts | |
| KR20190003092A (en) | Composition for preventing, improving or treating stress and depression comprising medicinal herb complex extract as effective component | |
| CN104784418A (en) | Medicine for curing protrusion of lumbar intervertebral disc | |
| CN103463628B (en) | A kind ofly to be used for the treatment of or the pharmaceutical composition of prophylactic treatment senile dementia and preparation thereof | |
| KR101167628B1 (en) | A composition comprising black ginseng for treating or preventing dementia and improving cognitive function | |
| CN105267711A (en) | Pharmaceutical preparation for treating vertigo | |
| CN110448649A (en) | The preparation process of eliminating pestilence and relieving toxicity particle | |
| CN104619331A (en) | Composition for brain-neuron protection and brain-disease prevention, alleviation or treatment comprising muskrat musk | |
| Ravash et al. | The effect of hydroalcoholic extracts from Taraxacum officinale on blood indicators of kidney and liver functions in male rats | |
| KR101161707B1 (en) | Composition for prevention or treatment allergy containing eriodyctiol | |
| CN105169064A (en) | Medicinal preparation for whitening skin | |
| CN103285188B (en) | Chinese medicine composition that a kind of vital energy benefiting and the kidney invigorating is invigorated blood circulation and preparation method thereof | |
| KR20230136879A (en) | Pharmacological Composition Comprising Lactic acid Bacteria Fermented Product of Morus alba Extract for Prevention or Treatment of Alzheimer's disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170822 Address after: Gyeonggi Do, South Korea Applicant after: Jia Quan institution of higher education Industry And School Cooperation Address before: Seoul, South Kerean Applicant before: CJ Corp. |
|
| TA01 | Transfer of patent application right | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150408 |
|
| RJ01 | Rejection of invention patent application after publication |