CN100546592C - The herb formulation that contains Herba Centellae and Semen Sesami as the brain-strengthening medicine - Google Patents

The herb formulation that contains Herba Centellae and Semen Sesami as the brain-strengthening medicine Download PDF

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CN100546592C
CN100546592C CNB200380111016XA CN200380111016A CN100546592C CN 100546592 C CN100546592 C CN 100546592C CN B200380111016X A CNB200380111016X A CN B200380111016XA CN 200380111016 A CN200380111016 A CN 200380111016A CN 100546592 C CN100546592 C CN 100546592C
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跑普·扑斯庞歌丹
千丹那·温卡特斯瓦·劳
拉马斯瓦米·卡蒂克
山塔·麦罗塔
拉杰·库马·戈尔
萨雅不拉塔·阿恰尔雅
马德哈万·索马纳塞恩
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Abstract

The invention provides a kind of new herb formulation, in order to improve memory, treat amnesia as the brain-strengthening medicine.Prescription is made up of the volatile oil of Semen Sesami (Centella asiatica) and the alcohol extract of Herba Centellae (Sesamum indium).Routinely, use with the dosage form of Emulsion or a kind of oral gelatin soft capsule.Semen Sesami is used for paralysis, the hyperfunction and dysmenorrhea of sexual function.Herba Centellae is used as the alternative medicine and the tonic of effective skin, nerve and hematologic disease.

Description

The herb formulation that contains Herba Centellae and Semen Sesami as the brain-strengthening medicine
Invention field:
A kind of novel collaborative herb formulation as the brain-strengthening medicine, it is used for improving cognition, memory ability and treatment amnesia and recovers thinking.
Background of invention and prior art
The discovery main in the neuroscience field of past 20 years is behavioristics, neurobiology and the cytology basis that the learning and memory process has been described.Brain is the neural set that is mutually related, and it is with a kind of dynamic and complicated form adjustment self and activity each other.The morphological properties of axoneure is very useful for the representation function feature.Study is defined as acquisition to information and technical ability, and subsequently the maintenance of these information is called as memory.In medical terminology, the destruction subsequently that information is preserved is called as " amnesia ".Therefore, multiple pharmaceutical preparation or brain injury are studied the influence of cognitive behavior, and quilt very is called learning and memory process " strengthen or worsen " exactly.Learning and memory both can be considered to psychological process also can be considered to the neural connective variation of synapse.The development of the amnesia model that causes of ischemia reliably is crucial for the functional outcome of analyzing the ischemia damage and the curative effect that detects potential medicine on the science.Medicinal plants is improving memory and is still being underestimated greatly as the effect of cerebral tonic object space face.In addition, some oils are found and as tranquilizer, central nervous system's stimulant, adaptogen, bronchodilator, antidepressants and muscle relaxants people such as (, 2000) Singh.In the early stage brain development process in late period in utero and birth back, central nervous system's choline function system plays an important role for learning and memory function, and the choline function of brain goes down and can cause dementia with as syndromes such as the loss of memory of cerebrovascular or Alzheimer's disease, disorientations.After the cerebral ischemia, the reduction of cerebral blood flow and blood oxygen amount can appear.Also have report, the memory that anoxia causes reduces relevant with the synthetic minimizing of acetylcholine (Gibson and Duffy, 1981) with judgment.Mainly, the principal character of animal and man memory formation is its progressive process from temporary transient unstable form to form steady in a long-term.In the process of this consolidation, memory may be destroyed by the multiple medicine that brings out amnesia.ECS, low temperature and anoxia all are the non-intervention type diagnostic methods, and it can cause that animal loses consciousness, bring out retrograde amnesia by the mechanism relevant with being applied to clinical medicine.Recapture hypothesis and think that the reagent that causes amnesia destroys the recovery of memory rather than the preservation of memory, because the reproduction that when the influence of some drugs weakens in time, can cause normal memory to keep.The consolidation of information is by the marginal texture mediation, and wherein particularly hippocampal formation has been brought into play crucial effect in memory is handled.Proposed the major avenues of approach in limbic system and the cortex structure, it is responsible for the nerve connections in the information process.Medicine has stimulation as containing the material of amfetamine and caffeine, having to memory.Therefore, studies show that this herb formulation has the function that promotes memory, it is used for the treatment of amnesia and can be used as the maincenter antioxidant as cerebral tonic.
The purpose of invention:
Main purpose of the present invention provides a kind of collaborative herb formulation, as the brain-strengthening medicine, is used to improve cognitive memory ability, recovers thinking, and can treat or prevent amnesia and have the promotion memory impairments as a kind of antioxidant.
Another object of the present invention provides a kind of method for preparing collaborative herb formulation, this herb formulation is as the brain-strengthening medicine, be used to improve cognitive memory ability, recover thinking, and can treat or prevent amnesia and have the promotion memory impairments as a kind of antioxidant.
Another object of the present invention provides a kind of purposes of collaborative herb formulation, this herb formulation is as the brain-strengthening medicine, be used to improve cognitive memory ability, recover thinking, and can treat or prevent amnesia and have the promotion memory impairments as a kind of antioxidant.
Brief summary of the invention:
The invention provides and a kind ofly treat effective herb formulation with the medical herbs dosage form, it comes from the seed oil of Semen Sesami (Sesamum indicum), and it is as brain-strengthening and improve the medicine of cognitive competence.This medical herbs oil contains sesamin, sesamolin, sesamol (a kind of phenol antioxidant), vitamin, protein and aminoacid.Oleum sesami can have pale red yellow to dark red xanchromatic difference aspect color.The Semen Sesami seed is used as nourishing food and flavoring agent.The Semen Sesami seed is used as emollient, diuretic, lactagogue and nutrient and healthcare products, it is reported to be used for the treatment of bleeding hemorrhoids that the extract of while Herba Centellae (Centilla asiatica) fresh leaf has the potential effect that enforces one's memory and we find that it can produce the abirritative effect.This extract contains Sen Tuoke acid (centoic acid), asiatic acid (centellic acid), oleic acid, linoleic acid, linolenic acid and Lin Ge acid (lingocericacid).It does the increase (Ayurveda) of treatment leukoderma, bronchitis, Kapha and spleen.It also is used as a kind of cardiac diuretic and is used for appetite strengthening (Yunani).It also demonstrates the remarkable facilitation to integration capability and way of act.
Detailed description of the invention
Semen Sesami (Sesamum indicum Linn.) section: Pedaliaceae (Pedaliacae)
The plant explanation:
Be typically found at warmer geographic a year of the big profit of Africa, Asia or Australia or perennial medical herbs or shrub.India has an appointment six kinds, and wherein Semen Sesami (Sesamum indicum) is extensively cultivated.Uprightly, branch or branch not, annual, the 60-180cm height is cultivated in whole India Plain and height above sea level and is up to 1,200m.Leaf 7.5cm-12.5cm, for single type, (or) when changing, upper leaf is narrow ellipticalness, middle leaf is an oval, zigzag, and the bottom leaf has division or bird foot shape (pedatisect).Flower has skin dark stain for white, pink colour or lavender Dao Pink, and axil has raceme, fruit capsule shape, and rectangular tetragon, some is flat a little, and four deep depressions are arranged, and length is 1.5~5cm.Seed is black, brown or white, long 2.5-3mm, wide 1.5mm (Wealth of India, 1992).
Medical applications:
The Semen Sesami seed is used as nutraceutical, also can be used as flavoring agent.When being used for food, must shell.The method of shelling is made up of the following step: seed is immersed in the cold water spends the night, then it is carried out drying and rub on coarse surface.Sesamin and sesamolin almost do not show antioxidant activity (Wealth of India, 1992).
Phytochemistry:
The edible oil seed of Semen Sesami (Sesamum indicum) is owing to its oil comes into one's own, and in the last few years, it had obtained extra attention as human nutrition material protein source.Its change color serve as reasons white through brown to black.Analysis for the general composition of the seed that grows in different regions, the world provides scope of data following (is unit with the g/100g dry seed): moisture content, 4.1-6.5; Ether extract, 43.0-56.8; Protein 17.6-26.4; Crude fibre 2.9-8.6; Carbohydrate 9.1-25.3; Also comprise vitamin, wherein vitamin B1 and niacin content are very abundant.Also comprise other vitamin such as vitamin B2, nicotinic acid, 80.0 in addition; Pantothenic acid, 9.5; Ascorbic acid with trace.Also comprise from the carbohydrate (% of dry thing) of the alcohol extract of the seed coarse powder of defat as glucose, 2.6; Sucrose, 0.57; Galactose, 1.1; Raffinose with trace.It contains important protein matter globulin (α and beta Globulin).Oleum sesami contains abundant oleic acid and linoleic acid, adds up to account for 85% of whole fat constituents.Submember to oil is studied, and its Main Ingredients and Appearance comprises sesamin and sesamolin, they in other vegetable oil, be not found and also the synergy that plays a role with insecticide relevant.Other chemical compounds such as sesamol (a kind of phenol antioxidant) are cleared existing usually with trace water.
Pharmacy:
Oleum sesami has the activity of antioxidant.The Semen Sesami seed is used as emollient, diuretic, lactagogue and nutrient and healthcare products.It is said that it helps to treat hemorrhoid, the blended ointment of seed and butter is used for bleeding hemorrhoids.It is said that the decoct of seed is an emmenagogue, and to the treatment cough effectively.Unite use with Semen Lini and can be used as estrualization agent.The plaster of making by the seed of grind up can be used for the treatment of burn, scald etc.The paste of seed is used for the treatment of ulcer.Pulverous seed can be used for the treatment of amenorrhea and dysmenorrhea (Kirt , ﹠amp; Basu, II, 1859; Nadkarni, I, 1128).
Herba Centellae (Centella asiatica) section: Umbelliferae (Umbelliferae)
The plant explanation:
The elongated draft of crawling.Stem is elongated, villous (prostate) in the axil of vertical tuber, and the palpus shape, blush, internode is long, on the root tight knot.Leaf diameter 1.3-6.3cm, the multi-disc leaf is given birth at the tuber place, and its handle that comes into leaves usually has 1-3 sheet leaf on the joint of each stem, circle or kidney shape are wider than length, more or less some depression, be entirely zigzag or shallow zigzag, both sides are all level and smooth, and many elongated veins are from the heart-shaped basal growth of leaf.Petiole is long to be about 7.5-15cm variation or more, tubulose, smoothly or almost level and smooth.Stipule is short, and is born in petiole formation sheath shape base portion.Umbel, its flower by 3-4 sheet pink colour, stockless (handle is not almost arranged) is formed; Anthocaulus is had fur or smooth, and short, pink avette petal has point, has 2 under each corymb.Calyx tooth 0, wherein petal is tiny, pink colour, avette band point.Fruit 4mm is long, grows up in wide, and avette, hard, its mesocarp is thick, and netted fold has permanent petal on the top usually, and elementary ridge and the boundary of secondary ridge are obviously.It is distributed in the tropical and subtropical zone area in India, Ceylon and the world.
Medical applications:
This plant is pungent, and bitter in the mouth is easy to digestion, relieving constipation, and cooling effect, analeptic, anti-heating, appetite stimulator (Yunani), treatment leukoderma, anemia, urinary incontinence, hematologic disease are used for the treatment of mental sickness (Ayurveda).This plant has niff, and nerve is had the hypnosis sedation, is used for cardiac tonic and brain-strengthening and removes noise; Treatment is had the hiccups, headache.This plant is used as the alternative medicine and the health medicine of a kind of effective skin, sacred disease.Some areas in India, people custom together make the powder of dried leaves and milk and are used for promoting integrated intelligence.It is reported that the leaf oral administration and externally is all effective for the syphilis dermatoses; At Maraba (malabar) seashore, this plant is as a kind of leprosy curative.This plant still is the common drug of the slight dysentery intestinal disorder of a kind of child of being used for the treatment of: three or four leaves with Fructus anethi (cumin) and sugar, are applied at umbilical part after smashing to pieces.At Kang Kan (konkan), stutter with one or two leaf treatment every morning; The juice of leaf is used for (general) treatment because the skin rash that heat in blood causes with Flos Epiphylli Oxypetali bark (Cadamba bark) and black Fructus anethi.
Phytochemistry:
The alcohol extract of medical herbs obtains a kind of green, essential oil, fatty oil, cupreol and a kind of resinoid of intensive medicinal herbs flavor is arranged.Fatty oil is made up of following: glyceride, linoleic acid, lignoceric acid, Palmic acid and stearic acid.From exsiccant plant, obtain a kind of hydration and examine enlightening element (hydrocortylin) alkaloid.Wei Lian (Vellarine) and pectic acid are present in leaf and the root.This plant also contains the ascorbic acid that concentration is 13.8mg%.From this plant, separate and obtain a kind of Asiaticoside glycosides.The main component of triterpene mixture is Sen Tuoke acid (centoic acid).
Pharmacy:
The common dosage of oral medication is 5-10 grain (grains), three times on the one.Bigger dosage, medicine are easy anesthetis, produce dizzy, sometimes the stupor.Alcohol extract produces the rat abirritative effect that makes.The lumbar injection maximal dose reaches still avirulence of 350mg/kg.Alcohol extract and the spontaneous contraction of aqueous extract opposing also cause the of flaccid muscles of ileum of exsomatizing.Find that alcohol extract has sedation to rat under toxicity dose.The glucosides fraction has sedation to rat.It has reduced intensity and has reduced rabbit and the shrinkage amplitude of the stripped ileum of albinism rat.Canis familiaris L. for anesthesia can produce slight respiratory irritation, hypotension and bradycardic effect.The alcohol extract of finding plant has the protozoacide activity of anti-Entamoeba histolytica (E.histolytica).(Wealth?of?India,1992,115-118;Kirtikar?andBasu,Indian?Medicinal?P;ant,Vol?5,2001p.219)。
Therefore, main embodiment of the present invention relates to and is used for a kind of collaborative herb formulation, and it can be treated or prevent amnesia and have the antioxidant that improves the memory effect as the medicine of brain-strengthening, raising cognition, recovery thinking.Described prescription comprise the Semen Sesami (Centella asiatica) of pharmaceutically acceptable amount and Herba Centellae (Sesamumindium) extract and can optional acceptable salt, carrier or diluent.
Another embodiment of the invention relates to preparation method, is used to prepare a kind of collaborative herb formulation, and it can be treated or prevent amnesia and have the antioxidant that improves the memory effect as the medicine of brain-strengthening, raising cognition, recovery thinking.Described method comprises the steps:
(a) in the aqueous solution of alcohol, the raw material from the resulting powder of leaf of Semen Sesami (Centella asiatica) seed and Herba Centellae (Sesamumindium) is extracted,
(b) extract of filtration step (a) is removed residue,
(c) with the filtrate that obtains in the step (b) be lower than under about 55 ℃ temperature concentrated freeze-dried, and
(d) carbohydrate of the plant extract that obtains in the step (c) and about 70% and about 12% alcohol are mixed and made into 100ml, to obtain this prescription.
Another embodiment of the invention relates to alcohol-water solution in step (a) and the step (b), and wherein alcohol-water solution is an ethanol.
Another embodiment of the invention relates to the aqueous solution of alcohol in the step (a), and wherein Chun aqueous solution is about 60%.
Another embodiment of the invention relates to alcohol-water solution in the step (a), and wherein Chun aqueous solution is about 50%.
Another embodiment of the invention relates to temperature, and wherein the temperature in the step (b) is about 50 ℃.
Another embodiment of the invention relates to carbohydrate, and wherein the carbohydrate in the step (d) is selected from sucrose or lactose.
Another embodiment of the invention relates to carbohydrate, and wherein the concentration of carbohydrate is about 66%.
Another embodiment of the invention relates to the purposes of herb formulation, it is as the medicine of brain-strengthening, raising cognition, recovery thinking, and can treat or prevent amnesia and have the antioxidant that improves memory effect and treatment or prevention mammal (particularly people) amnesia, wherein said purposes comprises: with the herb formulation and pharmaceutically acceptable salt, carrier or the diluent co-administered chosen wantonly of the extract of Herba Centellae (Centella asiatica) and Semen Sesami (Seasmum indicum).
Another embodiment of the invention relates to Semen Sesami (Seasmum indicum) oil and Herba Centellae (Centella asiatica) oil, wherein the oily scope of Semen Sesami (Seasmum indicum) is about 2-20%, and the oily scope of Herba Centellae (Centella asiatica) is about 1-15%.
Another embodiment of the invention relates to Semen Sesami (Seasmum indicum) oil and Herba Centellae (Centella asiatica) oil, and wherein Semen Sesami (Seasmum indicum) oil is for being 10% approximately, and Herba Centellae (Centella asiatica) oil is 5%.
The extract that another embodiment of the invention relates to fill a prescription, wherein said prescription comprise that Semen Sesami (Seasmum indicum) oil is about 4%, Herba Centellae (Centella asiatica) oil about 2%.
Another embodiment of the invention relates to pharmaceutically acceptable diluent, carrier and salt, and it is selected from the group that comprises lactose, mannitol, sorbitol, microcrystalline Cellulose, sucrose, sodium citrate, sodium chloride or dicalcium phosphate.
Another embodiment of the invention relates to prescription, and wherein said prescription has high anti-oxidation, brings down a fever, lubricate, the effect of diuresis and the nerve of releiving.
Another embodiment of the invention relates to prescription, and wherein said prescription can discharge with capsule, tablet, syrup, suspensoid, pill or elixir form.
The extract that another embodiment of the invention relates to fill a prescription, the extract of wherein said prescription are to obtain from the seed of leaf of Herba Centellae (Centella asiatica) and Semen Sesami (Seasmum indicum).
Another embodiment of the invention relates to plant part, and wherein plant part is selected from by white and the seed of black kind and the group that leaf is formed.
The purposes that another embodiment of the invention relates to fill a prescription, wherein said prescription are to be used for the treatment of migraine, dizzy, leukoderma, anemia and appetite strengthening.
Another embodiment of the invention relates to prescription, and wherein prescription can also can be used for treating leprosy by for oral administration and external curing wound, fracture, syphilis dermatoses, improves disease and improves patient's health status.
Another embodiment of the invention relates to prescription, and wherein said prescription is used to alleviate hemorrhoid and gastropathy pain and spleen invigorating.
The dosage that another embodiment of the invention relates to fill a prescription, wherein said prescription dosage does not demonstrate the unusual of locomotor activity in about 20-110mg/kg scope the time, in the passive avoidance test, demonstrate significant and dose-dependent activity, demonstrate significant and dose-dependent antioxidant activity for brain frontal cortex and striatum zone.
The dosage that another embodiment of the invention relates to fill a prescription, wherein said prescription dosage does not demonstrate the dystropy of locomotor activity in about 25-100mg/kg scope the time, in the passive avoidance task, demonstrate significant and dose-dependent activity, demonstrate significant and dose-dependent antioxidant activity for brain frontal cortex and striatum zone.
Another embodiment of the invention relates to prescription, wherein fills a prescription and shortened incubation period in about 0.05-2.0 scope of second.
Another embodiment of the invention relates to prescription, wherein fills a prescription and shortened incubation period in about 0.18-1.22 scope of second.
Another embodiment of the invention relates to prescription, and wherein said prescription has reduced wrong number in the scope of about 1-35.
Another embodiment of the invention relates to prescription, and wherein said prescription has reduced wrong number in the scope of about 6.1-27.
Another embodiment of the invention relates to prescription, and wherein said prescription has improved body weight in the scope of about 140-170 gram.
Another embodiment of the invention relates to prescription, and wherein said prescription has improved body weight in the scope of about 141.6-168.7 gram.
Another embodiment of the invention relates to prescription, and wherein said prescription has increased kidney in the scope of about 0.80-1.5 gram heavy.
Another embodiment of the invention relates to prescription, and wherein said prescription has increased kidney in the scope of about 0.82-1.03 gram heavy.
Another embodiment of the invention relates to prescription, and wherein said prescription has increased liver in the scope of about 4-7 gram heavy.
Another embodiment of the invention relates to prescription, and wherein said prescription has increased liver in the scope of about 5.26-6.42 gram heavy.
Another embodiment of the invention relates to prescription, and wherein said prescription has increased spleen in the scope of about 0.60-0.80 gram heavy.
Another embodiment of the invention relates to prescription, and it is heavy to have increased spleen in the scope of the about 0.63-0.76 gram of described therein prescription.
Another embodiment of the invention relates to prescription, and wherein said prescription has reduced the activity of lipid peroxidation enzyme (LPO) in brain frontal cortex and striatum zone in the scope of 1.0-5.0 under no pressure condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has reduced the activity of lipid peroxidation enzyme (LPO) in brain frontal cortex and striatum zone in the scope of 0.74-3.48 under no pressure condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has strengthened the activity of catalase (CAT) in brain frontal cortex and striatum zone in the scope of 22-40 under no pressure condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has strengthened the activity of catalase (CAT) in brain frontal cortex and striatum zone in the scope of 24.5-35.3 under no pressure condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has strengthened the activity of peroxide dismutase (SOD) in brain frontal cortex and striatum zone in the scope of 22-40 under no pressure condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has strengthened the activity of peroxide dismutase (SOD) in brain frontal cortex and striatum zone in the scope of 23.2-30.3 under no pressure condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has under stress reduced the activity of lipid peroxidation enzyme (LPO) in brain frontal cortex and striatum zone in the scope of about 1-7.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has under stress reduced the activity of lipid peroxidation enzyme (LPO) in brain frontal cortex and striatum zone in the scope of about 2.8-4.86.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has strengthened the activity of catalase (CAT) in brain frontal cortex and striatum zone in the scope of 10-25 under long-term stress condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has strengthened the activity of catalase (CAT) in brain frontal cortex and striatum zone in the scope of 12.4-22.5 under long-term stress condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has reduced the activity of peroxide dismutase (SOD) in brain frontal cortex and striatum zone in the scope of 20-35 under long-term stress condition.
Another embodiment of the invention relates to prescription, and wherein said prescription dosage has reduced the activity of peroxide dismutase (SOD) in brain frontal cortex and striatum zone in the scope of 21-33 under long-term stress condition.
Of the present invention being combined as has synergistic combination, shown unexpected characteristic.In fact, this combination not merely is the mixture that only shows its constitutive property adduction.On the other hand, it provides the beat all reinforced effects of each constitutive property, and this is non-obvious.
The example that below provides illustrates the present invention, therefore should not be understood that limitation of the scope of the invention.
Embodiment
Embodiment 1
By following non-limiting example the present invention is carried out deep explanation.
Prescription (F1)
Semen Sesami (Seasmum indicum) 2 weight %
Sucrose/lactose 66.7g/1.2g
Alcohol 10 weight %
Water polishing 100ml
Prescription (F2)
Herba Centellae (Centella asiatica) 2 weight %
Sucrose/lactose 66.7g/1.2g
Alcohol 10 weight %
Water polishing 100ml
Prescription (F3)
Semen Sesami (Seasmum indicum) 4 weight %
Herba Centellae (Centella asiatica) 2 weight %
Sucrose/lactose 66.7g/1.2g
Alcohol 10 weight %
Water polishing 100ml
Select Semen Sesami (Seasmum indicum) and Herba Centellae (Centella asiatica) and dry in the shade for use.Exsiccant raw material (1Kg) is pulverized, and extracted 5 days with 50% alcoholic acid aqueous solution (3L).Afterwards, solution is poured out and is filtered (if necessary) to remove its residue.Extracting solution is concentrated in being lower than 50 ℃ vacuum, then the extracting solution lyophilizing is obtained Powdered extract.
Plant extract is mixed, be dissolved in 10% the 500ml ethanol, filtering solution also adds a certain amount of sugar, and heating is until sugar dissolving cooling and volume is supplemented to 100ml with the water of aequum then.
This prescription is very effective for strengthening brain and improving cognitive competence.Therefore, describe research in detail, provided the using method and the type of the prescription and the standardization edible oil of each component for peroral dosage form.
Locomotor activity (Lucomoter Activity):
Adopt spacious measuring locomotor activity.The device that is provided with in sound damping darkroom is an open place (end diameter 60cm; High 50cm).The bottom surface equal portions are 19 parts.Put a 100W bulb apart from bottom surface 80cm place, every rat is placed in place central authorities, every their spontaneous behaviour of 5min record (walking about with static).
Passive avoidance task (diving tower experiment, Step-Down Test):
The experiment of diving tower passive avoidance is by utilizing the diving tower device to carry out, and the diving tower device is made of the chest of 5 * 25 * 40cm, and base plate is become by the stainless (steel) wire lattice of diameter 2mm spacing 8mm, is placed with a rubber platform (diameter 4cm, high 4cm) in a corner of grid.Carry out electricity irritation by the pulse electric shock device that links to each other with grid.After cerebral ischemia/hyoscyamine of 24hr (Scopalamine) (0.4mg/kg, lumbar injection) is handled, obtain experiment (acquisition test).In experiment, every rat is placed on the platform gently, allow it be familiar with environment freely 3 minutes, give then and grid base plate electric shock (4mA).If rat jumps off from platform, electric shock will pass to the rat on the grid base plate so.Be 2 minutes break time.Obtain experiment and keep experiment (retention test) after 24 hours.Once more every rat is placed on the platform.Rat flees back the time (incubation period) of not having the electric shock zone from electrical network record.If rat did not jump off from platform in 2 minutes, then stop to keep experiment, long latency is designated as 2 minutes.Rat jumps off from platform and then is designated as mistake, writes down wrong number in 2 minutes.
The long-term stress that foot electric shock (footshock) is brought out:
That uses grid base plate in the lucite box carries out the electric shock of 1 hour every day to rat, continues 21 days.The persistent period of each electric shock and electric shock blanking time, random arrangement was 3-5s and 10-110s separately, separated cerebral tissue and obtained following maincenter antioxidase (table 5-6)
Table 1: prescription F1 obtains the influence of damage for the memory of rat in the diving tower experiment
P: compare with matched group c<0.001
P: compare with the hyoscyamine group x<0.01, y<0.001
Attention: in the process of using Semen Sesami (Seasmum indicum) oil to treat, do not observe death/significantly unusual.
Prescription F1 includes only Oleum sesami.
The result of table 1 shows that the behavior mistake number of animal is with the corresponding minimizing of dosage.And hyoscyamine treatment group demonstrates significantly increasing of wrong number.Therefore the F1 that fills a prescription makes prolongation of latency and shows significant effect.
Table 2: prescription F2 obtains the influence of damage for the memory of rat in the diving tower experiment
Figure C20038011101600201
P: compare with matched group c<0.001
P: compare with the hyoscyamine group x<0.05, y<0.01
Attention: in the process of using the prescription do not comprise Semen Sesami (Seasmum indicum) oil to treat, do not observe death/significantly unusual.
Prescription F2 includes only Herba Centellae.The result demonstrates the remarkable minimizing of wrong number, but the wrong number of observation table 1 discovery prescription F1 is less than prescription F2.And hyoscyamine treatment group demonstrates significantly increasing of wrong number.
Table 3: prescription F3 obtains the influence of damage for the memory of rat in the diving tower experiment
Figure C20038011101600202
P: compare with matched group c<0.001
P: compare with the hyoscyamine group x<0.01, y<0.01
Attention: comprise in use and not observe death/significantly unusual in the process that the prescription of Semen Sesami (Seasmum indicum) oil treats.
Prescription F3 comprises Semen Sesami (Seasmum indicum) and Herba Centellae (Centella asiatica).
The result of table 3 demonstrates the very significant effect relevant with dosage.But better therapeutic is arranged the tacrine of positive control (Tacrine) but it is very important as synthetic drug for the side effect of multiple receptor saturation.Use the animal groups of hyoscyamine treatment to demonstrate the loss of memory and the wrong negativity result who increases.Therefore compare with prescription F2 (table 2) with prescription F1 (table 1), prescription F3 demonstrates synergy.
Tacrine (Tacrine) (1,2,3,4-tetrahydrochysene-5-aminacrine or THA) (people such as Summers, Clinical Tox 1980; 16 (3): 269-281) more effective and be used to treat Alzheimer's disease for the memory ability that improves the Alzheimer's disease patient, but it can not be cured this disease and can cause gastropathy, vomiting, diarrhoea, pyrosis, myalgia, headache and lose appetite etc.
Table 4: prescription F3 is for the influence of the relevant meansigma methods ± SEM of rat body weight
Figure C20038011101600211
Prescription F3 comprises Semen Sesami (Seasmum indicum) and Herba Centellae (Centella asiatica).
The weight that the result of table 4 is presented at various vitals in the toxicity research does not significantly change.
Therefore the F3 that fills a prescription has significant curative effect and safety.
Attention: comprise in use and not observe death/significantly unusual in the process that the prescription of Semen Sesami (Seasmum indicum) oil treats.
Table 5: the prescription F3 long-term stress (CS) that damage is brought out for the brain frontal cortex and the influence of peroxide dismutase (SOD), catalase (CAT) and lipid peroxidation enzyme (LPO) level
Figure C20038011101600221
P: I compares with group a<0.05, b<0.01
P: IV compares with group x<0.05, y<0.01, z<0.001
Numerical value is the mean value SEM of every group of 6 Mus
Group II and group III and group I are relatively
Group V and group VI and group IV are relatively
Prescription F3 comprises Semen Sesami (Seasmum indicum) and Herba Centellae (Centella asiatica).
The result of table 5 demonstrates obvious antioxidation activity, shows as when using prescription F3 and use prescription F3 under long-term stress condition, and the level of catalase in the brain frontal cortex (CAT) and oxide dismutase (SOD) raises.Lipid peroxidation enzyme (LPO) product is eliminated in the prescription F3 of high dose, and level reduces.Therefore the F3 that fills a prescription shows the antioxidant activity in the brain frontal cortex.
Attention: in the process of using Semen Sesami (Seasmum indicum) oil to treat, do not observe death/significantly unusual.
Table 6: the striatum zone damage that prescription F3 brings out for long-term stress (CS) and the influence of peroxide dismutase (SOD), catalase (CAT) and lipid peroxidation enzyme (LPO) level
Figure C20038011101600231
P: I compares with group *<0.05, *<0.01
P: compare with group V and group VI *<0.05, *<0.001
Numerical value is the mean value SEM of every group of 6 Mus
Group II and group III and group I are relatively
Group V and group VI and group IV are relatively
The result shows, the prescription F3 that comprises Semen Sesami (Seasmum indicum) and Herba Centellae (Centella asiatica) has obvious antioxidation activity, and when under long-term stress condition, using the F3 that fills a prescription (organizing V and group VI), by removing lipid peroxidation enzyme (LPO) free radical and making the rising of catalase (CAT) and oxide dismutase (SOD) level show obvious antioxidation activity.
Attention: comprise in use and not observe death/significantly unusual in the process that the prescription of Semen Sesami (Seasmum indicum) oil treats.
List of references
1.6,187,313 Feb.,2001Segelman
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13.So people such as Ra Kim, Cognitive Brain Research, 17, pp.454-461,2003.
14.Tzen Deng people .Plant Physiol, 101 (1), pp.267-276,1993.
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Claims (78)

1. one kind is used as brain-strengthening, improves cognitive, as to recover thinking medicine and is used as the collaborative medical herbs that can treat or prevent amnesia and have the antioxidant of raising memory effect, described collaborative medical herbs comprises extract and optional pharmaceutically acceptable salt, carrier or the diluent of 2-20% Semen Sesami and 1-15% Herba Centellae.
2. collaborative medical herbs according to claim 1, wherein seed of Sesamum indicum L. extract is 10%, Herba Centellae extract is 5%.
3. collaborative medical herbs according to claim 1, wherein seed of Sesamum indicum L. extract is 4%, Herba Centellae extract is 2%.
4. collaborative medical herbs according to claim 1, pharmaceutically acceptable salt wherein, carrier or diluent are selected from the group that comprises lactose, mannitol, sorbitol, microcrystalline Cellulose, sucrose, sodium citrate, sodium chloride or dicalcium phosphate.
5. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs can discharge with capsule, tablet, syrup, suspensoid, pill or elixir form.
6. collaborative medical herbs according to claim 1, the extract of wherein said collaborative medical herbs are to obtain from the seed of leaf of Herba Centellae and Semen Sesami.
7. according to claim 1 or 6 described collaborative medical herbs, wherein plant part is selected from by white and the seed of black kind and the group that leaf is formed.
8. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs dosage does not demonstrate the unusual of locomotor activity in the 20-110mg/kg scope time, in the passive avoidance test, demonstrate significant and dose-dependent activity, demonstrate significant and dose-dependent antioxidant activity for brain frontal cortex and striatum zone.
9. collaborative medical herbs according to claim 8, wherein said collaborative medical herbs dosage does not demonstrate the dystropy of locomotor activity in the 25-100mg/kg scope time, in the passive avoidance task, demonstrate significant and dose-dependent activity, demonstrate significant and dose-dependent antioxidant activity for brain frontal cortex and striatum zone.
10. collaborative medical herbs according to claim 1, wherein collaborative medical herbs has reduced the damage that memory is obtained by shortened incubation period in the 0.05-2.0 scope of second.
11. collaborative medical herbs according to claim 10, wherein collaborative medical herbs has reduced the damage that memory is obtained by shortened incubation period in the 0.18-1.22 scope of second.
12. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs has reduced the damage that memory is obtained by reduced wrong number in the scope of 1-35.
13. collaborative medical herbs according to claim 12, wherein said collaborative medical herbs has reduced the damage that memory is obtained by reduced wrong number in the scope of 6.1-27.
14. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs has increased body weight in the scope of 140-170 gram.
15. collaborative medical herbs according to claim 14, wherein said collaborative medical herbs has increased body weight in the scope of 141.6-168.7 gram.
16. the described collaborative medical herbs of claim 1, wherein said collaborative medical herbs have increased kidney in the scope of 0.8-1.5 gram heavy.
17. collaborative medical herbs according to claim 16, wherein said collaborative medical herbs have increased kidney in the scope of 0.82-1.03 gram heavy.
18. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs have increased liver in the scope of 4-7 gram heavy.
19. collaborative medical herbs according to claim 18, wherein said collaborative medical herbs have increased liver in the scope of 5.26-6.42 gram heavy.
20. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs have increased spleen in the scope of 0.60-0.80 gram heavy.
21. collaborative medical herbs according to claim 20, wherein said collaborative medical herbs have increased spleen in the scope of 0.63-0.76 gram heavy.
22. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs under no pressure condition, have reduced the activity of lipid peroxidation enzyme in brain frontal cortex and striatum zone in the scope of 1.0-5.0.
23. collaborative medical herbs according to claim 22, wherein said collaborative medical herbs under no pressure condition, have reduced the activity of lipid peroxidation enzyme in brain frontal cortex and striatum zone in the scope of 0.74-3.48.
24. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs under no pressure condition, have strengthened the activity of catalase in brain frontal cortex and striatum zone in the scope of 22-40.
25. collaborative medical herbs according to claim 24, wherein said collaborative medical herbs under no pressure condition, have strengthened the activity of catalase in brain frontal cortex and striatum zone in the scope of 24.5-35.3.
26. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs under no pressure condition, have strengthened the activity of peroxide dismutase in brain frontal cortex and striatum zone in the scope of 22-40.
27. collaborative medical herbs according to claim 26, wherein said collaborative medical herbs under no pressure condition, have strengthened the activity of peroxide dismutase in brain frontal cortex and striatum zone in the scope of 23.2-30.3.
28. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs are under stress, reduced the activity of lipid peroxidation enzyme in brain frontal cortex and striatum zone in the scope of 1-7.
29. collaborative medical herbs according to claim 28, wherein said collaborative medical herbs are under stress, reduced the activity of lipid peroxidation enzyme in brain frontal cortex and striatum zone in the scope of 2.8-4.86.
30. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs has strengthened the activity of catalase in brain frontal cortex and striatum zone in the scope of 10-25 under long-term stress condition.
31. collaborative medical herbs according to claim 30, wherein said collaborative medical herbs has strengthened the activity of catalase in brain frontal cortex and striatum zone in the scope of 12.4-22.5 under long-term stress condition.
32. collaborative medical herbs according to claim 1, wherein said collaborative medical herbs has reduced the activity of peroxide dismutase in brain frontal cortex and striatum zone in the scope of 20-35 under long-term stress condition.
33. collaborative medical herbs according to claim 32, wherein said collaborative medical herbs has reduced the activity of peroxide dismutase in brain frontal cortex and striatum zone in the scope of 21-33 under long-term stress condition.
34. one kind is used to prepare the described collaborative medical herbs method of claim 1, described method comprises the steps:
(a) in the aqueous solution of alcohol, the raw material from the resulting powder of leaf of Semen Sesami seed and Herba Centellae is extracted,
(b) extract of filtration step (a) is removed residue,
(c) with the filtrate that obtains in the step (b) be lower than under 55 ℃ the temperature concentrated freeze-dried, and
(d) disaccharidase of the plant extract that obtains in the step (c) and 70% and 12% alcohol are mixed and made into 100ml, to obtain this collaborative medical herbs, wherein, described collaborative medical herbs comprises the extract of 2-20% Semen Sesami and 1-15% Herba Centellae.
35. method according to claim 34, wherein the aqueous solution of the alcohol in the step (a) is 60%.
36. method according to claim 35, wherein the aqueous solution of the alcohol in the step (a) is 50%.
37. method according to claim 34, wherein the aqueous solution of the alcohol in the step (a) is an ethanol.
38. method according to claim 34, wherein the temperature in the step (b) is 50 ℃.
39. method according to claim 34, wherein the disaccharidase in the step (d) is selected from sucrose or lactose.
40. according to claim 34 or 39 described methods, wherein the concentration of disaccharidase is 66%.
41. method according to claim 34, wherein the alcohol in the step (d) is 10%.
42. method according to claim 34, wherein seed of Sesamum indicum L. extract is 2-20%, and Herba Centellae extract is 1-15%.
43. according to the described method of claim 42, wherein seed of Sesamum indicum L. extract is 10%, Herba Centellae extract is 5%.
44. according to the described method of claim 42, wherein seed of Sesamum indicum L. extract is 4%, Herba Centellae extract is 2%.
45. method according to claim 34, wherein said collaborative medical herbs have strong anti-oxidation, bring down a fever, lubricate, diuresis and the neural effect of releiving.
46. method according to claim 34, wherein said collaborative medical herbs can be with capsule, tablet, syrup, suspensoid, pill or elixir form administration.
47. method according to claim 34, wherein plant part is selected from by white and the seed of black kind and the group that leaf is formed.
48. any described collaborative medical herbs is in preparation brain-strengthening, cognitive, the recovery thinking of raising among the claim 1-33, and treatment or prevention amnesia and improve purposes in the medicine of memory effect, wherein said purposes comprises: administration has the extract of Herba Centellae and Semen Sesami and the collaborative medical herbs of optional pharmaceutically acceptable salt, carrier or diluent.
49. according to the described purposes of claim 48, wherein said purposes also comprises the purposes of described collaborative medical herbs in the medicine of preparation treatment migraine, dizzy, leukoderma, anemia and appetite strengthening.
50. according to the described purposes of claim 48, wherein said purposes comprises that also described collaborative medical herbs passes through to take orally and external curing wound, fracture, syphilis dermatoses in preparation, the treatment leprosy is improved disease and is improved purposes in patient's the medicine of health status.
51. according to the described purposes of claim 48, wherein said purposes comprises that also described collaborative medical herbs alleviates purposes in the medicine of hemorrhoid and gastropathy pain and spleen invigorating in preparation.
52. according to the described purposes of claim 48, pharmaceutically acceptable salt wherein, carrier or diluent are selected from the group that comprises lactose, mannitol, sorbitol, microcrystalline Cellulose, sucrose, sodium citrate, sodium chloride or dicalcium phosphate.
53. according to the described purposes of claim 48, wherein said collaborative medical herbs dosage does not demonstrate the unusual of locomotor activity in the 20-110mg/kg scope time, in the passive avoidance test, demonstrate significant and dose-dependent activity, demonstrate significant and dose-dependent antioxidant activity for brain frontal cortex and striatum zone.
54. according to the described purposes of claim 48, wherein said collaborative medical herbs dosage does not demonstrate the dystropy of locomotor activity in Herba Centellae 25-100mg/kg scope the time, in the passive avoidance task, demonstrate significant and dose-dependent activity, demonstrate significant and dose-dependent antioxidant activity for brain frontal cortex and striatum zone.
55. according to the described purposes of claim 48, wherein collaborative medical herbs has reduced the damage that memory is obtained by shortened incubation period in the 0.05-2.0 scope of second.
56. according to the described purposes of claim 55, wherein collaborative medical herbs has reduced the damage that memory is obtained by shortened incubation period in the 0.18-1.22 scope of second.
57. according to the described purposes of claim 48, wherein said collaborative medical herbs has reduced the damage that memory is obtained by reduced wrong number in the scope of 1-35.
58. according to the described purposes of claim 57, wherein said collaborative medical herbs has reduced the damage that memory is obtained by reduced wrong number in the scope of 6.1-27.
59. according to the described purposes of claim 48, wherein said collaborative medical herbs has increased body weight in the scope of 140-170 gram.
60. according to the described purposes of claim 59, wherein said collaborative medical herbs has increased body weight in the scope of 141.6-168.7 gram.
61. according to the described purposes of claim 48, wherein said collaborative medical herbs has increased kidney in the scope of 0.8-1.5 gram heavy.
62. according to the described purposes of claim 61, wherein said collaborative medical herbs has increased kidney in the scope of 0.82-1.03 gram heavy.
63. according to the described purposes of claim 48, wherein said collaborative medical herbs has increased liver in the scope of 4-7 gram heavy.
64. according to the described purposes of claim 63, wherein said collaborative medical herbs has increased liver in the scope of 5.26-6.42 gram heavy.
65. according to the described purposes of claim 48, wherein said collaborative medical herbs has increased spleen in the scope of 0.60-0.80 gram heavy.
66. according to the described purposes of claim 65, wherein said collaborative medical herbs has increased spleen in the scope of 0.63-0.76 gram heavy.
67. according to the described purposes of claim 48, wherein said collaborative medical herbs has reduced the activity of lipid peroxidation enzyme in brain frontal cortex and striatum zone in the scope of 1.0-5.0 under no pressure condition.
68. according to the described purposes of claim 67, wherein said collaborative medical herbs has reduced the activity of lipid peroxidation enzyme in brain frontal cortex and striatum zone in the scope of 0.74-3.48 under no pressure condition.
69. according to the described purposes of claim 48, wherein said collaborative medical herbs has strengthened the activity of catalase in brain frontal cortex and striatum zone in the scope of 22-40 under no pressure condition.
70. according to the described purposes of claim 69, wherein said collaborative medical herbs has strengthened the activity of catalase in brain frontal cortex and striatum zone in the scope of 24.5-35.3 under no pressure condition.
71. according to the described purposes of claim 48, wherein said collaborative medical herbs has strengthened the activity of peroxide dismutase in brain frontal cortex and striatum zone in the scope of 22-40 under no pressure condition.
72. according to the described purposes of claim 71, wherein said collaborative medical herbs has strengthened the activity of peroxide dismutase in brain frontal cortex and striatum zone in the scope of 23.2-30.3 under no pressure condition.
73. according to the described purposes of claim 48, wherein said collaborative medical herbs has under stress reduced the activity of lipid peroxidation enzyme in brain frontal cortex and striatum zone in the scope of 1-7.
74. according to the described purposes of claim 73, wherein said collaborative medical herbs has under stress reduced the activity of lipid peroxidation enzyme in brain frontal cortex and striatum zone in the scope of 2.8-4.86.
75. according to the described purposes of claim 48, wherein said collaborative medical herbs has strengthened the activity of catalase in brain frontal cortex and striatum zone in the scope of 10-25 under long-term stress condition.
76. according to the described purposes of claim 75, wherein said collaborative medical herbs has strengthened the activity of catalase in brain frontal cortex and striatum zone in the scope of 12.4-22.5 under long-term stress condition.
77. according to the described purposes of claim 48, wherein said collaborative medical herbs has reduced the activity of peroxide dismutase in brain frontal cortex and striatum zone in the scope of 20-35 under long-term stress condition.
78. according to the described purposes of claim 77, wherein said collaborative medical herbs has reduced the activity of peroxide dismutase in brain frontal cortex and striatum zone in the scope of 21-33 under long-term stress condition.
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GB2427549A (en) 2007-01-03
CN1953760A (en) 2007-04-25
AU2003298474A1 (en) 2005-08-12
JP4624263B2 (en) 2011-02-02
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