CN101548981A - Application of ginsenosides Rg1, Rh1 and Ppt to resistance of cognitive competence and study memory function disorders - Google Patents
Application of ginsenosides Rg1, Rh1 and Ppt to resistance of cognitive competence and study memory function disorders Download PDFInfo
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Abstract
The invention discloses an application of ginsenoside Rg1, Rh1 and Ppt to the resistance of cognitive competence and study memory function disorders, in particular relates to an application of ginsenoside Rg1 and/or metabolites thereof, such as Rh1 and/or Ppt to the preparation of medicines and health products preventing, relieving and/or curing diseases or symptoms capable of causing the cognitive competence disorders and/or the study memory function disorders, particularly the Alzheimer's disease (AD). The invention is applied to the preparation of the medicines and the health products improving the cognitive competence and the study memory function.
Description
Technical field
The present invention relates to ginsenoside Rg1's metabolite Rh1 and improving learning and memory behavioristics and improving the neural plasticity effect and the effect of Rg1 raising neural plasticity of Ppt.The present invention relates to ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt is used for preventing, alleviates and/or treat and can cause cognitive function and/or damage in learning and memory such as Alzheimer ' s disease disease or the medicine of symptom or the purposes of health product such as (AD, Alzheimers); Also relate to and contain described ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt and be used for preparation prevention, alleviate and/or treatment Alzheimer ' s disease (AD, Alzheimer) disease or symptom such as are particularly improved the purposes of the medicine and/or the pharmaceutical composition of cognitive function and/or learning and memory function;
Background technology
Ginsenoside (ginsenoside) is one of main component of Radix Ginseng, many kinds of ginsenoside monomers of separation and Extraction to 40 from Radix Ginseng at present, be divided three classes by its chemical constitution: 20 (s)-protopanoxadiol types (20s-Protopanxadiol), 20 (s)-Protopanaxatriol types (20s-Protopanxatriol) and oleanolic acid type (oleanolic acid).The ginsenoside Rg1 belongs to 20 (s)-Protopanaxatriol type saponin, it is the significant composition of Radix Ginseng, it also is the topmost active ingredient of Radix Ginseng, this composition can extract from root, stem, leaf and the Radix Panacis Quinquefolii of Radix Ginseng and Radix Notoginseng, existing process has reached the feather weight level of production, but still fails so far to synthesize successfully.Its structure and relevant biological activity wide coverage in relevant textbook and scientific literature.But ginsenoside Rg1's metabolism in the human gastrointestinal tract is ginsenoside Rh1 and Ppt, and structure as shown in Figure 1.
The ginsenoside Rg1 has biologic activity widely, and the bright ginsenoside Rg1 of inventor's employee's card in the past is the main effective ingredient of Radix Ginseng nootropic effect.Rg1 has anti-aging effects old Mus, and immunological enhancement has anti-apoptotic effect on several apoptosis models, and proof has anti-amnesia effect on tens kinds of dysmnesia models.Neural plasticity plays an important role in regulation and control brain function and control nervous system disease process.Wherein synaptic plasticity is to find it also is most important neural plasticity form the earliest, enhancing, the synapse long time journey transmitted as basic synapse strengthen inducing of (LTP) and keep with learning and memory closely related, the neurobiology basis that is considered to learning and memory is listed in an important indicator estimating cognitive function.The inventor studies have shown that mechanism that the ginsenoside Rg1 significantly improves learning and memory function is to improve basic synapse transmission, induce LTP to form and strengthen inducing mutually and keeping mutually of the inductive LTP of HFS.The inventor has applied for that the ginsenoside Rg1 is used for disease or the purposes of symptom and the patent that is used to improve cognitive function of anti-cerebral ischemia and/or cerebral ischemia initiation.The inventor has applied for that the ginsenoside Rg1 is used for disease or the purposes of symptom and the patent that is used to improve the cognitive function effect of anti-cerebral ischemia and/or cerebral ischemia initiation, and this application is at ginsenoside Rg1's metabolite Rh1 and the effect of Ppt and the raising neural plasticity effect of Rg1.
But ginsenoside Rg1's metabolite Rh1 and Ppt regulate the synaptic plasticity effect and improve cognitive function and learning and memory function aspect effect and with not the appearing in the newspapers more so far of prototype Rg1 action intensity.
In addition, about ginsenoside's research, there is a controversial problem in academia always, and promptly the ginsenoside is that prototype plays a role or its metabolite plays a role.A kind of view thinks that ginsenoside's prototype carries the glycan molecule of different numbers (from a part sugar to five molecular saccharides), and these glycan molecules and biologic activity have important related; Another kind of view thinks that the ginsenoside is a kind of prodrug (pro-drug), and it just plays a role after being transformed into metabolite in vivo, is any actually view correct? the new conclusion that the present invention finds and proposes.
Summary of the invention
One aspect of the present invention relates to and is selected from the ginsenoside Rg1, and particularly the active component of ginsenoside Rg1's metabolite Rh1 and/or Ppt improves the purposes that mammal basis synapse is transmitted.Among the present invention, the basic synapse transfer function of described raising is meant increases mammal (1/30Hz under basic electrophysiological stimulation condition, intensity adopts 1/2 the current intensity cause maximum PS amplitude as testing stimulus intensity, and runs through whole test, and stimulating the square wave ripple wide is 0.2ms.Carry out automatic record analysis by computer, calculate the PS amplitude as the excitatoty index of DG granular cell group), the PS amplitude increases to some extent, but increases the purposes less than 30%.
One aspect of the present invention relates to and is selected from the ginsenoside Rg1, and particularly the active component of ginsenoside Rg1's metabolite Rh1 and/or Ppt is induced the purposes that forms LTP.Among the present invention, described inducing forms LTP effect and is meant under basic electrophysiological stimulation condition (the same), and the PS amplitude of rat has increased by 30% or above and kept at least 30 minutes, promptly induces the purposes of formation LTP.
In one aspect of the invention, the active component that relates to the metabolite Ppt that is selected from ginsenoside Rg1, ginsenoside Rg1 is used for strengthening and keeps that (high-frequency stimulation, HFS) inductive LTP keeps the purposes of phase by high frequency stimulation.
In the present invention, described HFS is very near the spontaneous activity of animal Hippocampus theta rhythm, the formation that can effectively induce hippocampal dentate LTP.Strengthen and keep and be meant mutually after HFS induces generation LTP and keeps 30min by keeping of the inductive LTP of HFS, (hippocampal dentate granular cell layer LTP is induced by the HFS of 10 string 100Hz to give different chemical compounds respectively, every train is stimulated by 5 wide square waves for 0.2ms of ripple to be formed, stimulus intervals is 200ms), promptly can strengthen HFS more stimulates the LTP that produces to keep the PS amplitude of phase, and continues at least 1.5 hours.
The inventor is by further studying beat all discovery to ginsenoside Rg1's metabolite Rh1 and ginsenoside Rg1's metabolite Ppt, above-mentioned metabolite self also has the basic synapse transfer function of enhancing respectively, and Ppt can also strengthen and consolidate the effect of keeping phase by the inductive LTP of HFS.
In one aspect of the invention, relate to a kind of pharmaceutical composition that basic synapse is transmitted that is used to improve, it contains the active component of at least a ginsenoside Rg1 of being selected from, ginsenoside Rg1's metabolite Rh1 and ginsenoside Rg1's metabolite Ppt, and optional, the acceptable excipient of pharmacy.
In one aspect of the invention, relate to a kind of pharmaceutical composition that the inductive LTP of HFS keeps phase that is used to consolidate, it contains the active component of at least a ginsenoside Rg1 of being selected from and ginsenoside Rg1's metabolite Ppt, and optional, the acceptable excipient of pharmacy.
In the present invention, described mammal especially preferably is the people.
One aspect of the present invention, relate to ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt and be used for prevention, alleviate and/or treat anti-Alzheimer ' s disease diseases such as (AD, Alzheimers) or symptom and the anti-purposes that can cause the medicine of cognitive dysfunction and/or damage in learning and memory in preparation.
In the present invention, described prevention, alleviation and/or treatment can cause the disease of cognitive dysfunction and/or damage in learning and memory such as Alzheimer ' s disease (AD, Alzheimer) etc. or symptom and be selected from and improve cognitive function and damage in learning and memory.
In the present invention, described prevention was meant before Alzheimer ' s disease diseases such as (AD, Alzheimers) occurring, suppressed the generation of diseases such as cognitive function and damage in learning and memory.Described alleviation is meant and is occurring improving cognitive function and damage in learning and memory in Alzheimer ' the s disease disease incidence processes such as (AD, Alzheimers).Described treatment be meant occur after Alzheimer ' the s disease diseases such as (AD, Alzheimers) or pathogenic process in, realize improving cognitive function and damage in learning and memory on the clinical meaning.
More specifically, the disease of prevention of the present invention, alleviation and/or treatment as Alzheimer ' s disease (AD, Alzheimer) etc. or symptom are prevention, alleviation and/or treat cognitive function and the damage in learning and memory that causes at disease.
Another aspect of the present invention, relate to and a kind ofly be used for prevention, alleviate and/or treatment can cause cognitive dysfunction and/or damage in learning and memory such as Alzheimer ' s disease (AD, Alzheimer) pharmaceutical composition of etc. disease or symptom, it contains ginsenoside Rg1 and/or its metabolite Rh1 and/or the Ppt of prevention or treatment effective dose, and optional pharmaceutically acceptable carrier and/or adjuvant.In the present invention, according to route of administration, described ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt pharmaceutical composition can be and be selected from following dosage form: solution, suspension, Emulsion, pill, capsule, powder, sustained release or extended release preparation.
Ginsenoside Rg1 of the present invention and/or its metabolite Rh1 and/or Ppt pharmaceutical composition can be prepared with known method, use several approach that the experimenter is used, include but not limited to parenteral, per os, part, Intradermal, intramuscular, intraperitoneal, subcutaneous, intranasal approach.
Ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt can prepare by commercially available or known method among the present invention.
What ginsenoside Rg1 of the present invention and/or its metabolite Rh1 and/or Ppt pharmaceutical composition were optional can prepare with one or more pharmaceutically acceptable carriers and/or excipient by any conventional method.Therefore, ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt and their the acceptable salt of pharmacy and solvate can be formulated as especially and for example suck or be blown into (through port or nose) or per os, containing, parenteral or rectally.That ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt can adopt is charged, the form of the neutral and/or acceptable salt of other pharmacy.The example of pharmaceutically acceptable carrier include but not limited to Remington ' s Pharmaceutical Sciences (A.R.Gennaro, Ed.), 20th edition, Williams﹠amp; Wilkins PA, those described in the USA (2000).
Ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt pharmaceutical composition also can adopt forms such as solution, suspension, Emulsion, pill, capsule, powder, sustained release or extended release preparation.These preparations will contain ginsenoside Rg1 and/or its metabolite Rh1 and/or the Ppt that treats effective dose, be preferably purified form, and an amount of carrier, so that the form to the suitable administration of patient to be provided.Preparation should be fit to administering mode.
In the present invention, the ginsenoside Rg1 of described purified form and/or its metabolite Rh1 and/or Ppt are meant pure basically ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt, especially purity is greater than 80%, preferably greater than 85%, particularly preferred greater than 90%, in addition preferred greater than 95% ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt.Concrete, the ginsenoside Rg1 of described purified form and/or its metabolite Rh1 and/or Ppt purity range can be 90%-98% for example.
Parenteral
Ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt pharmaceutical composition can be formulated as by injection for example by injecting parenteral.The preparation that is used for injecting can be present in ampoule or the multi-dose container that contains the optional antiseptic that adds with unit dosage forms.Parenteral administration can be included in ampoule, disposable syringe or the multi-dose vials of being made by glass, plastics etc.Preparation can adopt the form such as the suspension in oiliness or aqueous carrier, solution or Emulsion, and can contain adjuvant, as suspending agent, stabilizing agent and/or dispersant.
For example, parenteral administration can be aseptic injectable solution or the suspension (for example, the solution in the 1,3 butylene glycol) in nontoxic parenteral acceptable diluent or solvent.Acceptable carrier and operable solvent comprise water, Ringer's solution and isotonic sodium chlorrde solution.In addition, routine uses aseptic fixed oil as solvent or suspension media.The fixed oil of any gentleness be can use for this purpose, synthetic monoglyceride and diglyceride comprised.In addition, in parenteral administration, also can use fatty acid such as oleic acid.
In addition, ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt pharmaceutical composition also can be formulated as powder type, rebuild with carrier that is fit to such as pyrogen-free sterilized water before use.For example, the ginsenoside Rg1 of suitable parenteral and/or its metabolite Rh1 and/or Ppt pharmaceutical composition can comprise the sterile isotonic saline solution, wherein contain ginsenoside Rg1 and/or its metabolite Rh1 and/or the Ppt of every volume 0.1% to 90% weight.For example, solution can contain has an appointment 5% to about 20%, more preferably about 5% to about 17%, and more preferably from about 8% to about 14%, more more preferably from about 10% ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt.Solution or powder formulation also can contain solubilizing agent and local anesthetic such as lignocaine, so that alleviate the pain of injection site.Other parenteral compound administration methods are known in the art, and within the scope of the invention.
Oral administration
For oral administration, ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt pharmaceutical composition can adopt tablet or capsular form, and it prepares with the acceptable excipient of pharmacy such as binding agent, filler, lubricant and disintegrating agent by conventional method.
A. binding agent
Binding agent (for example includes but not limited to corn starch, potato starch or other starch, gelatin, natural and paragutta such as arabic gum, sodium alginate, alginic acid, other alginate, powdered tragacanth, guar gum, cellulose and derivant thereof, ethyl cellulose, cellulose acetate, carboxymethylcellulose calcium, sodium carboxymethyl cellulose), polyvinylpyrrolidone, methylcellulose, pregelatinized starch, hydroxypropyl emthylcellulose (for example, Nos.2208,2906,2910), microcrystalline Cellulose and composition thereof.The form of suitable microcrystalline Cellulose comprises, for example, (can be with the material that AVICEL-PH-101, AVICEL-PH-103 and AVICEL-PH-105 sell from FMC Corporation, American Viscose Division, Avicel Sales, Marcus Hook, Pennsylvania, USA).An example of suitable bonding is that FMCCorporation is with the microcrystalline Cellulose of AVICEL RC-581 sale and the mixture of sodium carboxymethyl cellulose.
B. filler
Filler includes but not limited to Talcum, calcium carbonate (for example granule or powder), lactose, microcrystalline Cellulose, Powderd cellulose, dextrates (dextrates), Kaolin, mannitol, silicic acid, sorbitol, starch, pregelatinized starch and composition thereof.
C. lubricant
Lubricant includes but not limited to calcium stearate, magnesium stearate, mineral oil, light mineral oil, glycerol, sorbitol, mannitol, Polyethylene Glycol, other ethylene glycol, stearic acid, sodium lauryl sulfate, Talcum, hydrogenated vegetable oil (for example, Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, Oleum helianthi, Oleum sesami, olive oil, Semen Maydis oil and Oleum Glycines), zinc stearate, ethyl oleate, ethyl laurate, agar and composition thereof.Other lubricant comprises, for example, (AEROSIL 200 for solid-state silica gel, Baltimore, Maryland, the W.R.GraceCo. of USA produces), the aerosol that condenses (the Deaussa Co.of Plano of synthetic silicon, Texas, the USA sale), CAB-O-SIL (Boston, Massachusetts, a kind of pyrogenicity silica product that the Cabot Co. of USA sells) and composition thereof.
D. disintegrating agent
Disintegrating agent includes but not limited to agar-agar, alginic acid, calcium carbonate, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, crospovidone, polacrilin potassium, primojel, Rhizoma Solani tuber osi or tapioca, other starch, pregelatinized starch, other starch, clay, other algin, other celluloses, natural gum and composition thereof.
Tablet or capsule can be randomly with method coatings well known in the art.If ginsenoside Rg1 of the present invention and/or its metabolite Rh1 and/or Ppt pharmaceutical composition use binding agent and/or filler, then they are generally prepared into about 50% chemical compound to about 99% weight.On the one hand, about 0.5% disintegrating agent to about 15% weight, particularly about 1% disintegrating agent to about 5% weight can be used in combination with ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt.Randomly can add lubricant, general about 1% weight of its amount less than ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt.Preparation technology of solid oral dosage form and pharmacy acceptable additive be at Marshall, S
OLIDO
RALD
OSAGEF
ORMS, (Banker and Rhodes Eds.), describe among the 7:359-427 (1979) ModernPharmaceutics.Other more atypical preparations are well known in the art.
Be used for the form that oral liquid preparation can adopt solution, syrup or suspension.Perhaps, liquid preparation can be the form of dry products, and water or suitable carriers are rebuild before use.These liquid preparations can (for example be used pharmacy acceptable additive such as suspending agent by conventional method, sorbitol syrups, cellulose derivative or hydrogenation edible fat), emulsifying agent (for example, lecithin or arabic gum), nonaqueous carrier (for example, almond oil, oily ester, ethanol or fractionated vegetable oil) and/or antiseptic (for example, methyl or propyl group P-hydroxybenzoic acid fat or sorbic acid) prepare.These preparations also can contain suitable buffer salt, flavoring agent, coloring agent, aromatic and sweeting agent.Be used for oral preparation and also can be formulated as the sustained release of realizing chemical compound.Oral formulations preferably contains 10% to 95% chemical compound.In addition, ginsenoside Rg1 of the present invention and/or its metabolite Rh1 and/or Ppt pharmaceutical composition also can be formulated as tablet or the lozenge that is used to containing administration with conventional method.Other oral administration methods of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt pharmaceutical composition are well known to a person skilled in the art, and within the scope of the invention.
The sustained release administration
For activity and the minimizing administration frequency that prolongs ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt, can prepare sustained release (or continuing to discharge) preparation.The sustained release preparation also can be used for influencing onset time or other features, as sanguification compound level, thereby influences the generation of side effect.
The sustained release preparation can be designed as a certain amount of ginsenoside Rg1 and/or its metabolite Rh1 and/or the Ppt that initial release produces required curative effect, discharge ginsenoside Rg1 and/or its metabolite Rh1 and/or the Ppt of other content gradually and continuously, so that in long-time, keep the curative effect level.In order to keep in vivo near constant chemical compound level, ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt can discharge from dosage form with certain speed, replace the ginsenoside Rg1 and/or its metabolite Rh1 and/or the Ppt that go out from internal metabolism and/or secretion.The sustained release of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt can be stimulated by multiple inducement, as, pH changes, variations in temperature, enzyme, water, or other physiological conditions or molecule.
Controlled Release System can comprise, for example, infusion pump, it can be used for the mode administered compound of carrying insulin or chemotherapeutics to certain organs or tumor to be similar to.Use this system, general and biodegradable, the biocompatible polymerization implant combined administration of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt, it discharges ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt in the time of control at position of selecting.The example of polymeric material comprises polyanhydride, poe, polyglycolic acid, polylactic acid, polyethylene vinyl acetate and copolymer and combination.In addition, controlled release system can place near the therapeutic goal, therefore only needs the part of whole-body dose.
Ginsenoside Rg1 of the present invention and/or its metabolite Rh1 and/or Ppt can be with well known to a person skilled in the art that other sustained release methods or doser use.Comprise, for example, hydroxypropyl emthylcellulose, other polymeric matrices, gel, permeable membrane, osmosis system, multiple coatings, microgranule, liposome, microsphere etc., perhaps any above-mentioned combination provides required release spectrum with different ratios.Other sustained release medications of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt are well known to a person skilled in the art, and within the scope of the invention.
Inhalation
Ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt also can use to lung by sucking directly.For inhalation, can easily ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt be transported to lung by many different devices.For example, metered dose inhaler (" MDI "), the jar of its use contains suitable low boiling propellant, and for example, dichlorodifluoromethane, Arcton 11, dichlorotetra-fluoroethane, carbon dioxide or other suitable gas can be used for directly carrying chemical compound to lung.The MDI device can obtain from many suppliers, for example 3M Corporation, Aventis, Boehringer Ingleheim, Forest Laboratories, Glaxo-Wellcome, Schering Plough and Vectura.
In addition, also can use Diskus (DPI) device to the lung administered compound.A kind of mechanism of the general use of DPI device, for example, the gas of outburst produces cloud form dry powder in container, can be sucked by the patient then.The DPI device also is well known in the art, can comprise available from many suppliers, for example, Fisons, Glaxo-Wellcome, Inhale Therapeutic Systems, ML Laboratories, Qdose and Vectura.A kind of universal version is multiple dose DPI (" MDDPI ") system, and it allows to use more than one therapeutic dose.The MDDPI device can be from obtaining such as the such company of AstraZeneca, GlaxoWellcome, IVAX, Schering Plough, SkyePharma and Vectura.For example, being used for the gelatine capsule of inhaler and insufflator and cartridge case can be formulated as and contain ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt and be applicable to the powder substrate of this system such as the mixture of powders of lactose or starch.
Can be used for device to another type of lung administered compound and be the liquid dispensing apparatus that AradigmCorporation for example provides.Liquid spray systems uses minimum nozzle to make the liquid compound atomizing, can directly be drawn in the lung then.For example, can use atomizer arrangement to the lung administered compound.Nebulizer for example by using ultrasonic energy, produces aerosol by the liquid compound preparation, forms the fine grained that is easy to suck.The example of nebulizer comprises the device that Sheffield/Systemic Pulmonary DeliveryLtd., Aventis and Batelle Pulmonary Therapeutics provide.
In another embodiment, can use Electrofluid Mechanics (" EHD ") aerosol device to the lung administered compound.The EHD aerosol device uses electric energy with liquid compound solution or suspension atomizing.When with the EHD aerosol device when lung is used this chemical compound, the electrochemical properties of compound formulation is the important parameter that will optimize.This optimization is undertaken by those skilled in the art's routine.Other feeding drug into pulmones methods of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt are well known to a person skilled in the art, and within the scope of the invention.
Be applicable to that the liquid ginsenoside Rg1 of nebulizer and liquid dispensing apparatus and EHD aerosol device and/or its metabolite Rh1 and/or Ppt preparation generally comprise ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt and pharmaceutically acceptable carrier.In a representative embodiment, pharmaceutically acceptable carrier is a kind of liquid, as alcohol, water, Polyethylene Glycol or perfluorocarbon.Randomly, can add the aerosol character that another material changes compound solution or suspension.For example, this material can be a liquid, as alcohol, glycol, Polyethylene Glycol or fatty acid.Preparation is applicable to that the liquid compound solution of aerosol device or the additive method of suspension are well known to a person skilled in the art.
The reservoir devices administration
Ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt also can be formulated as the reservoir devices preparation.Such durative action preparation can be by implanting (for example subcutaneous or intramuscular) or passing through administered intramuscular.Therefore, chemical compound can be prepared with suitable polymerization or hydrophobic material, as the Emulsion in acceptable oil or ion exchange resin, perhaps as the derivant of microsolubility such as the salt of microsolubility.Other reservoir devices medications of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt are well known to a person skilled in the art, and within the scope of the invention.
Topical
For topical, ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt can with carrier combinations so that send effective dose, according to required activity, effective dose is for example 1.0 μ M to 1.0mM.In one aspect of the invention, the pharmaceutical composition of topical can be applied to skin.Carrier can be, such as but not limited to the form of ointment, emulsifiable paste, gel, pastel, foam, aerosol, suppository, pad or gelling rod.
Topical formulations also can comprise the chemical compound for the treatment of effective dose in the acceptable excipient of ophthalmology such as buffer saline, mineral oil, vegetable oil such as Semen Maydis oil or Oleum Arachidis hypogaeae semen, vaseline, Miglyol 182, alcoholic solution or liposome or liposome sample product.Any of these chemical compound also can comprise antiseptic, antioxidant, antibiotic, immunosuppressant and other do not have the biology or the pharmacy efficacious agents of illeffects to this chemical compound.Other local administration method of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt are well known to a person skilled in the art, and within the scope of the invention.
Other drug-supplying systems
Various other drug-supplying systems are well known in the art, can be used for using chemical compound of the present invention.And these and other drug-supplying systems can unite and/or change, and optimize the administration of ginsenoside Rg1 of the present invention and/or its metabolite Rh1 and/or Ppt.
Another aspect of the present invention also relates to a kind of food, and it contains ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt.
Of the present inventionly relate in one aspect to a kind of prevention, alleviation again and/or treat anti-Alzheimer ' s disease (AD, Alzheimer) disease or symptom and anti-ly can cause the disease of cognitive dysfunction and/or damage in learning and memory or the method for symptom such as comprise to ginsenoside Rg1 and/or its metabolite Rh1 and/or the Ppt of patient's administering therapeutic effective dose of needs or contain the ginsenoside Rg1 that treats effective dose and/or the pharmaceutical composition of its metabolite Rh1 and/or Ppt.
In the present invention, the ginsenoside Rg1 of described treatment effective dose and/or its metabolite Rh1 and/or Ppt can be the arbitrary amount between the 0.5-200mg/kg body weight, be preferably the 1-150mg/kg body weight, 2-100mg/kg body weight more preferably, 3-50mg/kg body weight more preferably, more preferably 4-35mg/kg body weight, the more preferably arbitrary amount between the 5-20mg/kg body weight.
Definite principle of treatment effective dose
The toxicity of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt and curative effect can be by being used to measure LD in cell culture or laboratory animal
50(50% colony's fatal dose) and ED
50The standard pharmaceutical procedures of (50% colony's dose therapeutically effective) is determined.Dosage ratio between toxicity and the curative effect is a therapeutic index, can be expressed as ratio LD
50/ ED
50
The data that obtain from cell culture test and zooscopy can be used for the mankind in preparation and use with other mammiferous dosage ranges.The dosage of ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt preferably has minimum toxicity or is not having the toxic ED of comprising
50Circulating plasma or the scope of other body-fluid concentrations in.
This dosage may change in this scope, depends on employed dosage form and route of administration.For ginsenoside Rg1 of the present invention and/or its metabolite Rh1 and/or Ppt, the treatment effective dose can be estimated according to cell culture test when beginning.Can in animal model, design dosage, to reach the IC that comprises that in cell culture, measures
50The circulating plasma concentration range of (reaching the test compounds concentration that the maximum symptom of half suppresses).Can utilize these information to determine useful dosage in human and other mammals more accurately.Ginsenoside Rg1 in the blood plasma and/or its metabolite Rh1 and/or Ppt level for example can be measured by high performance liquid chroma-tography.
Can with the amount of the ginsenoside Rg1 of pharmaceutically acceptable carrier combination results one-pack type and/or its metabolite Rh1 and/or Ppt according to the host who is treated and concrete mode of administration and different.Those skilled in the art are to be understood that, the unit content of contained ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt does not need itself to constitute the treatment effective dose in indivedual dosage of each dosage form, because can be by using the treatment effective dose that a plurality of indivedual dosage reach to be needed.The dosage form of use, the disease of being treated and the specific purposes that will reach according to those skilled in the art's decision are depended in the selection of dosage.
Dosage with ginsenoside Rg1 of the present invention and/or its metabolite Rh1 and/or Ppt treatment disease or disease is selected according to multiple factor, the type, age, body weight, sex, diet and the medical condition that comprise the patient, route of administration, pharmacology's Consideration, pharmacokinetics and toxicology as activity, effectiveness, employed particular compound distribute, and whether use ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt drug-supplying system.Therefore, the actual dosage that uses may be very different between experimenter and experimenter.
Description of drawings
Fig. 1: the structural formula of ginsenoside Rg1 and metabolite Rh1 and Ppt.
2: the index determining a that brings out current potential: stimulus artifact, the starting point of b:EPSP, the mid point of c:b and d, the starting point of d:PS (end points at first positive peak), the peak point of e:PS (negative peak point), f: second positive peak point, g: through the vertical line of e and the intersection point of tangent line df, L
1: the OL of PS, L
2: the peak incubation period of PS.
Fig. 3. mice water maze device diagram: 1,2,3,4 is cecum 1,2,3,4, and the rank of organizing a performance, the lower right corner in labyrinth are terminal point
The specific embodiment
The concrete demonstration of following embodiment application of the present invention.But present embodiment does not limit the scope of application of the present invention.
Purpose: observe ginsenoside Rg1 and metabolite Rh1 thereof and Ppt induce formation to basic synapse transmission and LTP effect.
1.1. material and method
1.1.1. laboratory animal SD rat, male (body weight 250-300 gram) purchased in Nat'l Pharmaceutical ﹠ Biological Products Control Institute (quality certification SCXK (capital) 2005-0004), and animal feeding replaces (12h: 12h) clean in the level Animal House ad lib drinking-water in light and shade.Animal began to experimentize after conforming in Animal House 5 days.
1.1.2. experimental apparatus SEN-7203 three road electronic stimulators: (Nihon Kohden Co., Japan), VC-11 memory oscilloscope: (the same), SS-202J stimulus isolator: (the same), SR-6N stereotaxic instrument (NarishigeCo., Japan).
1.1.3. experimental technique
1.1.3.1. electrode is embedding
Animal is anaesthetized with urethane and chloral hydrate (1: 5 volume ratio) and is fixed on the stereotaxic instrument, remove periosteum with 3% hydrogen peroxide, determine stimulating electrode (two pieces of spacing 0.5mm with reference to Pellegrino rat brain stereotaxic atlas, cover the teflon insulation layer outward, most advanced and sophisticated exposed 0.2mm, the stainless pin formation of diameter 0.15mm), the accurate position at recording electrode (stainless pin of diameter 0.15mm constitutes for outer insulating layer coating, most advanced and sophisticated exposed 0.2mm) and intracerebroventricular injection position.The position of bipolar stimulation electrode is entorhinal area anterior perforated substania path (Perforantpath, PP) between fiber, its elements of a fix are AP-7.5mm, L4.2mm, H3.0mm, recording electrode is imbedded in homonymy hippocampal dentate granular cell layer, and its coordinate is AP-3.8mm, L2.5mm, H3.5mm, tricorn administration fistula is positioned at AP1.8mm, L0.8mm, H3.5mm.Be drilled to aperture at above-mentioned anchor point with bone drill, broken gently meninges puts down recording electrode and fistula according to vertical coordinate.Stimulating electrode then puts down 2.5mm earlier, and then slowly adjusts the position and induce the maximum cluster spike potential up to the stimulation with a constant intensity (Population spike in the time of PS) fixes electrode.
1.1.3.2. bring out the record of current potential and the computational methods of amplitude thereof
Adopt the extracellular recording method.After testing stimulus (ripple is wide to be the square wave stimulation of 0.2ms) is produced by electronic stimulator, transfer to PP through stimulus isolator and stimulating electrode, the action potential that brings out shows on memory oscilloscope through biological amplifier, and import computer simultaneously and carry out automatic record analysis, with the PS amplitude that calculates as the excitatoty index of DG granular cell.The testing stimulus frequency is 1/30Hz, and stimulus intensity then adopts 1/2 the current intensity that causes the required stimulus intensity of maximum PS as testing stimulus intensity, and runs through whole experiment, no longer changes.The measuring method of PS amplitude is got the vertical dimension (eg) of negative sense peak point e to the 1 and the 2nd forward peak point d and f line as shown in Figure 2.
1.1.3.3. medication and dosage
In order directly and promptly to observe the pharmacological action of chemical compound, we give ginsenoside Rg1, Rh1 and Ppt and normal saline matched group respectively by the conduit of implanting tricorn in this experiment.The thin plastic pipe that will connect microsyringe imports in the conduit, and stable certain hour writes down the PS of 30min again, represent the preceding basic synapse transmission of administration, in 5min medicine or the normal saline solvent of 10 μ l is slowly injected tricorn then.After the injection, thin plastic pipe is kept somewhere in conduit until the experiment end.Inject the back and continue to write down 1 hour to observe medicine for the influence of basic synapse transmission and the effect of inducing LTP to form.
Drug dose is that the densitometer of medicine in cerebral tissue calculates when being 2mL according to the rat brain volume.Like this, when giving 4 * 10 of 10 μ L
-5During the medicine of mol/L, its final concentration in cerebral tissue then is 2 * 10
-7Mol/L.
1.1.3.4. the analysis of data and statistics
Each testing stimulus all brings out a PS, with the PS amplitude of the meansigma methods after continuous 5 PS amplitudes stack as this time point.Every meansigma methods of 5min record, is basic synapse transmission level with 6 meansigma methodss that record with 30min before the administration, and the synapse transmission level of each time point is to compare relative amplitude (%) expression that draws with foundation level afterwards.Be abscissa at last with time, the relative amplitude of PS (%) is drawn the dynamic change figure of PS amplitude for vertical coordinate.All numerical value all adopt mean and standard error to represent that (Mean ± SEM), analytical method adopts variance analysis (ANOVA).
1.2. result
Ginsenoside Rg1 and metabolite Rh1 thereof and/or Ppt are to the influence of basic synapse transmission and the effect of inducing formation LTP
By table 1 as seen, the PS amplitude before and after the administration of the anesthetized rat ventricles of the brain changes, ginsenoside Rg1 and metabolite Rh1 thereof and Ppt (2 * 10
-7Mol/L, i.c.v.) compare with matched group (N.S.), can significantly strengthen basic synapse transmission, the enhancing amplitude is all greater than 30%, and all continue 30min at least, illustrate that the three all can strengthen basic synapse transmission and induce generation LTP, and the effect of metabolite Rh1 and Ppt all is better than prototype Rg1.N=6, Mean ± SEM, * P＜0.01vs matched group.
Table 1. ginsenoside Rg1 and metabolite Rh1 thereof and Ppt are to the influence of basic synapse transmission and the effect (n=6) of inducing formation LTP
1.3 conclusion:
The ginsenoside Rg1 of same concentrations and metabolite Rh1 thereof and Ppt all can improve basic synapse transmission and induce formation LTP, promptly has the effect that improves cognitive function and learning and memory function under the physiological status, has treatment again as Alzheimer ' s disease (AD, Alzheimer) etc. can cause the effect of the disease or the symptom of cognitive dysfunction and damage in learning and memory, and the effect of metabolite Rh1 and Ppt is imitated powerful in prototype Rg1.
Purpose: ginsenoside Rg1 and metabolite Ppt thereof keep the consolidation effect of phase to the inductive LTP of high frequency stimulation
2.1. material and method
Laboratory animal and experimental apparatus are all with embodiment 1.
Experimental technique
Embedding, the record that brings out current potential of electrode and the computational methods of amplitude thereof and data analysis and statistics are all with embodiment 1.
The tetanic stimulation parameter: hippocampal dentate granular cell layer LTP is induced by the HFS of 10 string 100Hz, and every train is by 5 wide 0.2ms of ripple, and frequency is that the square wave of 100Hz is formed, and train is spaced apart 200ms, and stimulus intensity is identical with testing stimulus.
When observing medicine, after inserting thin plastic pipe and stablize 30min, give high frequency stimulation for the influencing of the inductive LTP of high frequency stimulation, write down 30min after intracerebroventricular give two chemical compounds and normal saline respectively.Continue record and observed the phase of influence medicine is kept to(for) the inductive LTP of high frequency stimulation in 1.5 hours.
2.2. result
Ginsenoside Rg1 and metabolite Ppt thereof are to the influence of the inductive LTP of high frequency stimulation
By table 2 as seen, before and after the administration of the anesthetized rat ventricles of the brain, the variation of the PS amplitude of the inductive LTP of high frequency stimulation, ginsenoside Rg1 and metabolite Ppt (2 * 10 thereof
-7Mol/L i.c.v.) compares with matched group (N.S.-HFS), can significantly strengthen the inductive LTP intensity of high frequency stimulation, and continue at least 1.5 hours, and the effect of metabolite Ppt is better than prototype Rg1.N=6, Mean ± SEM,
#P＜0.01vsN.S.,
*P＜0.01vs matched group (N.S.-HFS).
Table 2. ginsenoside Rg1 and metabolite Ppt thereof keep the influence (n=6) of phase to the inductive LTP of high frequency stimulation.
2.3 conclusion:
The ginsenoside Rg1 of same concentrations and metabolite Ppt thereof all can strengthen and consolidate high frequency stimulation induce formation LTP keep phase, has the effect that improves cognitive function and learning and memory function, has treatment Alzheimer ' s disease (AD, Alzheimer) disease or symptom and anti-ly can cause the medicine disease of cognitive dysfunction and/or damage in learning and memory or the effect of symptom such as, and the effect of metabolite Ppt is imitated powerful in prototype Rg1.
From the electrophysiological index of The above results reflection as seen, ginsenoside Rg1 and/or its metabolite Rh1 and/or Ppt can significantly strengthen the synapse transmission of rat basis, induce and form LTP, and ginsenoside Rg1 and metabolite Ppt thereof can significantly strengthen the inductive PS amplitude of HFS, and consolidate it and keep the phase effect.
The improvement effect of the memory dysfunction that embodiment 3 ginsenoside Rg1s and metabolite Rh1 thereof and Ppt cause scopolamine
Purpose: observe the effect of the memory dysfunction that ginsenoside Rg1 and metabolite Rh1 thereof and Ppt cause scopolamine
3.1. material and method
3.1.1. laboratory animal KM mice, male (body weight 18-22 gram), purchase in Institute of Experimental Animals, Chinese Academy of Medical Sciences (quality certification SCXK (capital) 2004-0001), animal feeding replaces (12h: 12h) clean in the level Animal House ad lib drinking-water in light and shade.Animal began to experimentize after conforming in Animal House 3 days.
3.1.2. experimental apparatus
Mice is kept away dark experimental record instrument (model PA M5, Taisho Pharmaceutical Co., Ltd, Japan).Mice water maze device (institute of Materia Medica,Chinese Academy of Medical Sciences).
3.1.3. reagent
Scopolamine is available from Sigma company.Ginsenoside Rg1, metabolite Rh1 and Ppt are all available from Jilin University, and purity is all greater than 90%.
3.1.4. experimental technique
3.1.4.1. dosage regimen
The KM mice is divided into matched group, scopolamine model group, ginsenoside Rg1 5mg/kg group, 10mg/kg group and 20mg/kg group at random, every group of 16 mices,
Wherein matched group, scopolamine model group set time every morning irritate stomach and give distilled water, and ginsenoside Rg1 5mg/kg group, 10mg/kg group and 20mg/kg group are according to dosage irritated stomach respectively and given the ginsenoside Rg1, and administration is 8 days altogether.The 3rd day scopolamine model group, ginsenoside Rg1 5mg/kg group, 10mg/kg group and 20mg/kg group respectively before training 20min give scopolamine (1mg/kg) and cause dysmnesia model, keep away dark experiment training then, (being administration the 4th day) carries out official testing behind the 24hr, and each mice incubation period and errors number respectively organized in record respectively.The 5th day to the 7th day scopolamine model group, ginsenoside Rg1 5mg/kg group, 10mg/kg group and 20mg/kg group respectively before training 20min give scopolamine (1mg/kg) and cause dysmnesia model, carry out the water maze laboratory training then, carried out formal water maze test on the 8th day, (being administration the 5th day to the 8th day) write down respectively and respectively organized each mice incubation period and errors number in 4 days of water maze training and testing.
The KM mice is divided into matched group, scopolamine model group, ginsenoside's metabolite Rh15mg/kg group, 10mg/kg group and Ppt 5mg/kg group, 10mg/kg group at random, every group of 16 mices, wherein matched group, scopolamine model group set time every morning irritate stomach and give distilled water, Rh15mg/kg group, 10mg/kg group and Ppt 5mg/kg group, 10mg/kg group, according to dosage irritate stomach respectively and give Rh1 and Ppt, administration is 3 days altogether.The 3rd day scopolamine model group, Rh15mg/kg group, 10mg/kg group and Ppt 5mg/kg group, 10mg/kg group respectively before training 20min give scopolamine (1mg/kg) and cause dysmnesia model, keep away dark experiment training then, carry out official testing behind the 24hr, each mice incubation period and errors number respectively organized in record respectively.
3.1.4.2. mice is kept away dark test
Experimental provision is a trained reflex case, is divided into light and shade two parts, has a small holes that mice can be had free passage in two Room, and the copper grid are arranged at the bottom of the case, and wherein the copper grid of bottom, darkroom pass to 36V voltage.During experiment mice put into bright chamber and darkroom dorsad, because of the mice dark and habit of getting into the cave in the family way, so can repeatedly pierce darkroom (this behavior is wrong reaction) at the experiment training period.Will be shocked by electricity when mice one enters into darkroom four-footed contact copper grid, it can manage to withdraw from the darkroom at once.During training in first day, the record mice entered the number of times in darkroom and enters the time (being incubation period) of camera bellows for the first time in 2 minutes.Do experiment after 24 hours again, observe that mice enters the time (being incubation period) of camera bellows and the number of times (being errors number) that mice enters camera bellows first in 5 minutes.
3.1.4.3. mice water maze test
(73cm * 42cm * 30cm) form wherein forms the labyrinth by some dividing plates, as shown in Figure 3 to water maze by a black lucite cuboid tank, wherein 1,2,3,4 is cecum 1,2,3,4, one jiao of rank of organizing a performance in labyrinth are terminal point, depth of water 20cm in the labyrinth, water temperature (24 ± 1) ℃.
The carrier frequency channel break of with dividing plate A point and B being ordered in first day in training, mice at first is placed in 10s on the step, make it understand the existence of this safety zone, then mice is put in starting point A, allow its free swimming, the time (being incubation period) of writing down its number of times that enters cecum 1 (being errors number) and climbing up safety bench first is if the person that do not find the step as yet in training time 2min, will be directed into the safety bench place, be designated as 2min its incubation period.Take a momentary rest after the training for the first time by with the quadrat method training for the second time, every mice is trained twice altogether.Train other mice successively.
In training second day places the B point with dividing plate, and the swimming starting point of mice is the B point, writes down the errors number that mice enters cecum 1,2,3 in the 2min respectively, climbs up the incubation period of safety bench first, the training 2 times continuously of every mice.If the person that can not find the step in 2min will be directed into terminal point, be designated as 2min its incubation period.
The swimming starting point of training the 3rd to the 4th day mice is the C point, and mice enters the errors number of cecum 1,2,3,4 and finds every mice incubation period of safety bench to train secondary continuously in the record 2min.
3.1.4.4. the analysis of data and statistics
All numerical value all adopt mean and standard deviation to represent that (Mean ± SEM), analytical method adopts T-test.
3.2. result
3.2.1. keep away in the dark experiment improvement effect of the memory dysfunction that the ginsenoside Rg1 causes scopolamine
Table 3. is kept away in the dark experiment, the improvement effect of the mouse memory obstacle that the ginsenoside Rg1 causes scopolamine.n＝16，Mean±SEM。
Annotate: compare with matched group
1)P＜0.05,
2)P＜0.01; Compare with the scopolamine group
3)P＜0.05,
4)P＜0.01
By table 3 as seen, three dosage groups of ginsenoside Rg1 are compared with model group, the incubation period that can significant prolongation enters the darkroom, reduce the errors number that enters the darkroom, to compare effect strong slightly with the positive drug donepezil, illustrates that the ginsenoside Rg1 can improve the mouse memory obstacle that is caused by scopolamine in keeping away dark experiment.
3.2.2. in the water maze laboratory, the improvement effect of the memory dysfunction that the ginsenoside Rg1 causes scopolamine
Amnemonic mice preclinical influence in water maze laboratory that table 4. ginsenoside Rg1 causes scopolamine.n＝16，Mean±SEM。
Annotate: compare with matched group
1)P＜0.01; Compare with the scopolamine group
2)P＜0.05,
3)P＜0.01
In table 5. water maze laboratory, the influence of the dysmnesia mouse wrong times that the ginsenoside Rg1 causes scopolamine.n＝16，Mean±SEM。
Annotate: compare with matched group
1)P＜0.01; Compare with the scopolamine group
2)P＜0.05,
3)P＜0.01
By table 4,5 as seen, three dosage groups of ginsenoside Rg1 are compared with model group, the 3rd day of water maze training, ginsenoside Rg1 20mg/kg group and donepezil 5mg/kg group can significantly shorten the incubation period of finding security platform, and ginsenoside Rg1 10mg/kg group reduces the errors number that enters cecum; The 4th day of water maze training, three dosage groups of ginsenoside Rg1 and donepezil 5mg/kg group can significantly shorten the incubation period of finding security platform, ginsenoside Rg1 10mg/kg group and 20mg/kg group can reduce the errors number that enters cecum, illustrate that the ginsenoside Rg1 can improve the mouse memory obstacle that is caused by scopolamine in water maze laboratory.
3.2.3. keep away in the dark experiment improvement effect of the memory dysfunction that ginsenoside Rg1's metabolite Rh1 and Ppt cause scopolamine
Table 6. is kept away in the dark experiment, the improvement effect of the memory dysfunction that ginsenoside Rg1's metabolite Rh1 and Ppt cause scopolamine.n＝16，Mean±SEM。
Annotate: compare with matched group
1)P＜0.01; Compare with the scopolamine group
2)P＜0.05,
3)P＜0.01
By table 6 result as seen, ginsenoside Rg1's metabolite Rh1 compares with the scopolamine model group with Ppt, the incubation period that can significant prolongation enters the darkroom, reduce the errors number that enters the darkroom, Rh1 10mg/kg group and Ppt 5,10mg/kg organize and the positive drug donepezil to compare effect strong slightly, explanation ginsenoside Rg1's in keeping away dark experiment metabolite Rh1 and Ppt can improve the mouse memory obstacle that is caused by scopolamine, and the effect of metabolite Ppt is better than Rh1.
3.3 conclusion:
The ginsenoside Rg1 keeps away in dark experiment and the water maze laboratory and metabolite Rh1 and Ppt keep away in the dark experiment mice and all can improve the mouse memory obstacle that is caused by scopolamine mice, and the effect of metabolic end product Ppt is better than Rh1.
The scientific meaning of this result of study
1.LTP formation and keep the raising of explanation synaptic plasticity, provide experimental basis and theoretical foundation for Rg1 and metabolite Rh1 thereof and Ppt improve cognitive function, also be that Chinese medicine Radix Ginseng nootropic effect has been made scientific explarnation.
2. the ginsenoside Rg1 is the prototype medicine, Rh1 and Ppt are the metabolites of Rg1 in the human body, studies have shown that metabolite has the effect similar to the prototype medicine, and be better than prototype medicine Rg1, show after Rg1 enters in the body and can be utilized fully, explained that why Rg1 dosage little (5-10mg/kg), gastrointestinal absorption but have efficient effect less, because prototype medicine and metabolite all have pharmacological action, no matter which kind of route of administration can both produce pharmacological action, and the time of eliminating in the body also obtained prolongation.
3. be that the prototype medicine plays a role or the arguement that metabolite plays a role to the ginsenoside, we have had new conclusion, and promptly prototype medicine and metabolite all have biologic activity.The strongest evidence is that administration can induce LTP to form in the brain, but cerebrospinal fluid can not change Rg1 into Ppt, only have the Rh1 of trace to find, and obviously this concentration of Rh1 is had no effect to LTP.And metabolite ginsenoside Rh1 and Ppt all have the effect that improves learning and memory function that more is better than Rg1 in the Animal Behavior Science experiment.
Claims (11)
1. the ginsenoside Rg1 is used for preventing, alleviate and/or treat the medicine that can cause cognitive dysfunction and/or damage in learning and memory disease or symptom or the application of health product in preparation.
2. according to the application of claim 1, it is characterized in that described to cause cognitive dysfunction and/or damage in learning and memory disease or symptom be Alzheimer.
3. the ginsenoside Rg1 prepares the medicine that improves cognitive function and/or learning and memory function or the application in the health product.
4. ginsenoside Rg1's metabolite Rh1 is used for preventing, alleviate and/or treat the medicine that can cause cognitive dysfunction and/or damage in learning and memory disease or symptom or the application of health product in preparation.
5. according to the application of claim 4, it is characterized in that described to cause cognitive dysfunction and/or damage in learning and memory disease or symptom be Alzheimer.
6. ginsenoside Rg1's metabolite Rh1 improves the medicine of cognitive function and/or learning and memory function or the application in the health product in preparation.
7. ginsenoside Rg1's Ppt is used for preventing, alleviate and/or treat the medicine that can cause cognitive dysfunction and/or damage in learning and memory disease or symptom or the application of health product in preparation.
8. according to the application of claim 7, it is characterized in that described to cause cognitive dysfunction and/or damage in learning and memory disease or symptom be Alzheimer.
9. ginsenoside Rg1's Ppt improves the medicine of cognitive function and/or learning and memory function or the application in the health product in preparation.
10. food, it contains ginsenoside Rg1's metabolite Rh1.
11. a food, it contains ginsenoside Rg1's metabolite Ppt.
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| CN2011103856087A Division CN102526071A (en) | 2008-03-31 | 2008-03-31 | Application of Ppt for resisting cognition and learning and memorial dysfunctions |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102771791A (en) * | 2012-08-13 | 2012-11-14 | 广州白云山和记黄埔中药有限公司 | Healthcare food and preparation method and application thereof |
| CN108741074A (en) * | 2018-06-04 | 2018-11-06 | 中国人民解放军空军航空医学研究所 | A kind of nutritional supplement improved and/or assist improving people and/or animal cognition function |
| CN110944655A (en) * | 2017-07-18 | 2020-03-31 | 森尼赛斯生命科学公司 | Compositions and methods for treating and preventing cognitive decline and protecting neuronal function |
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2008
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102771791A (en) * | 2012-08-13 | 2012-11-14 | 广州白云山和记黄埔中药有限公司 | Healthcare food and preparation method and application thereof |
| CN110944655A (en) * | 2017-07-18 | 2020-03-31 | 森尼赛斯生命科学公司 | Compositions and methods for treating and preventing cognitive decline and protecting neuronal function |
| CN108741074A (en) * | 2018-06-04 | 2018-11-06 | 中国人民解放军空军航空医学研究所 | A kind of nutritional supplement improved and/or assist improving people and/or animal cognition function |
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Open date: 20091007 |