CN100525809C

CN100525809C - Medicinal composition of milkvetch root, chinaroot greenbrier and Hong Jingtian and its making method

Info

Publication number: CN100525809C
Application number: CNB2006101634724A
Authority: CN
Inventors: 黄振华
Original assignee: Shandong Xuanzhu Pharma Co Ltd
Current assignee: Haian Su Fu Technology Transfer Center Co Ltd
Priority date: 2005-12-05
Filing date: 2006-12-04
Publication date: 2009-08-12
Anticipated expiration: 2026-12-04
Also published as: CN1981857A

Abstract

A Chinese medicine for improving cerebral function and preventing cerebra ischemic or anoxic injury, senile dementia and vascular dementia is prepared from astragalus root, rhodiola root and Chinaroot greenbrier rhizome or their extracts. Its preparing process is also disclosed.

Description

Pharmaceutical composition of making by the Radix Astragali, Radix Rhodiolae and Rhizoma Smilacis Chinensis and preparation method thereof

1, technical field

The invention belongs to medical technical field, relate to a kind of pharmaceutical composition of mainly making by the Radix Astragali or its extract, Radix Rhodiolae or its extract and Rhizoma Smilacis Chinensis or its extract, and preparation method thereof and be used for improving the application of the medicine of brain function in preparation.

2, background technology

Disordered brain function comprises cerebral tissue ischemia or anoxia-induced apoptosis, memory disorder, dementia etc.Cerebral tissue is very responsive to ischemia, anoxia.Along with social senescence trend and the prolongation of the average life span, the sickness rate of ischemic cerebrovascular obviously rises, and the serious harm human health brings heavy burden for society and family.Cerebral ischemia and again the cognitive dysfunction that causes of perfusion also be subject to people's attention day by day.Memory disorder comprises that hypomnesis and memory are low inferior.Dementia is common senile disease, also is the difficult treatment that current the world of medicine generally acknowledges.According to World Health Organization (WHO), among the old people of over-65s, have people's intelligence of 10% obstacle to occur, and wherein dementia takes place 60% people, and with advancing age, dementia incidence rate is the trend that rises significantly.Senile dementia can be divided into chronic and acute two big classes according to the speed of symptom development, and wherein chronic dementia accounts for about 80%, comprises alzheimer disease, vascular dementia and both simultaneous Combination dementias.Cause that the dull-witted cause of disease has a lot, wherein most importantly Alzheimer (AD) and vascular dementia (VD), vascular dementia mainly is by caused by cerebrovascular disease.Dull-witted is modal performance with memory disorder.At present, the medicine that is used to improve brain function is more, but general prescription is more single, is difficult to have many-sided synergism, can not have simultaneously and strengthen brain function, delay brain aging, improve dementia symptom and improve the effect of intelligence, and accumulate poisoning and side effect take place in life-time service easily.

The Radix Astragali is the dry root of leguminous plant Radix Astagali Astragalus membranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao or Radix Astragali Astragalus membranaceus (Fisch.).Sweet in the mouth, warm in nature, return lung, spleen channel, have the effect of invigorating QI to consolidate the body surface resistance, diuresis detoxification, evacuation of pus, expelling pus and promoting granulation.The main effective ingredient of the Radix Astragali is astragalus polysaccharides and Radix Astragali total saponins.The modern pharmacology experiment shows that Radix Astragali extract has protective effect to rat and mouse brain ischemia-reperfusion, can improve the mice oxygen-resistant ability, can improve the ability of learning and memory and the immunologic function of immunosuppressed mice.

Radix Rhodiolae is the dry root and rhizome of Crassulaceae plant Radix Rhodiolae Rhodiola crenulata (Hook.F.et Thoma) H.Ohba.Sweet in the mouth, hardship, property is flat, returns lung, heart channel, the effect that has benefiting QI for activating blood circulation, promotes blood circulation and relieving asthma.Radix Rhodiolae contain the various active composition, main effective ingredient is rhodioside, butyl alcohol and rhodosin etc.The modern pharmacology experiment shows that Radix Rhodiolae has functions such as resisting fatigue, defying age, antioxidation, can improve the mice oxygen-resistant ability; Radix Rhodiolae extract can improve the learning capacity of mice; Rhodosin has obvious aging resistance effect to old rats, and the Alzheimer disease model rat is had control, protection and dementia effect.

Rhizoma Smilacis Chinensis is the dry rhizome of liliaceous plant Rhizoma Smilacis Chinensis Smilax china L..Sweet in the mouth, little bitterness, property is flat, returns liver, kidney channel, has the effect of expelling wind and removing dampness, detoxifcation dissipating blood stasis.The main effective ingredient of Rhizoma Smilacis Chinensis is a Rhizoma Smilacis Chinensis total saponins, comprises dioscin, diosgenin, Sarsasapogenin, Smilagenin etc.The modern pharmacology experiment shows that Rhizoma Smilacis Chinensis has good antiinflammatory action, and is effective to Alzheimer.

At present, utilize the interaction of the Radix Astragali or its extract, Radix Rhodiolae or its extract, Rhizoma Smilacis Chinensis or its extract, composition of prescription, preparation is used to improve the medicine of brain function, does not appear in the newspapers as yet.

3, summary of the invention

In order to meet clinical needs; improve the disordered brain function patient's quality of life; the invention provides a kind of pharmaceutical composition of improving brain function and preparation method thereof that is mainly used in; mainly make by the Radix Astragali or its extract, Radix Rhodiolae or its extract and Rhizoma Smilacis Chinensis or its extract; cerebral ischemia or cerebral anoxia damage there is remarkable protective effect; can significantly improve the ability of learning and memory of alzheimer disease, vascular dementia rats, produce beyond thought effect.

Pharmaceutical composition of the present invention is made by the Radix Astragali, Radix Rhodiolae and Rhizoma Smilacis Chinensis, its parts by weight are: 400～10000 parts of the Radixs Astragali, 100～2000 parts of Radix Rhodiolaes, 150～3000 parts of Rhizoma Smilacis Chinensiss, be preferably 1000～5000 parts of the Radixs Astragali, 200～1000 parts of Radix Rhodiolaes, 300～1500 parts of Rhizoma Smilacis Chinensiss, more preferably 2000 parts of the Radixs Astragali, 400 parts of Radix Rhodiolaes, 600 parts of Rhizoma Smilacis Chinensiss.

The Radix Astragali in the pharmaceutical composition of the present invention, Radix Rhodiolae, Rhizoma Smilacis Chinensis can with The suitable solvent and method separately or mixed extraction processing obtain extract, total extract is made clinically arbitrary or pharmaceutically acceptable dosage form with mixing acceptable accessories again." extract separately " and be meant that the Radix Astragali, Radix Rhodiolae, each flavor medical material of Rhizoma Smilacis Chinensis extract separately by different technology respectively and obtain extract, each extract are mixed obtaining total extract again." mixed extraction " is meant, the Radix Astragali, Radix Rhodiolae, Rhizoma Smilacis Chinensis three flavor medical materials extract together and obtain total extract; Perhaps two flavor medical materials wherein extract together and obtain extract, mix obtaining total extract again with the extract of another flavor medical material.Main effective ingredient in the total extract of gained is Radix Astragali total saponins, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins, perhaps be astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins, the total content of main effective ingredient is not less than 30%, preferably is not less than 50%.

In the extraction preparation method of the above-mentioned Radix Astragali, Radix Rhodiolae, Rhizoma Smilacis Chinensis, used solvent is meant solvent pharmaceutically commonly used, can be water or ethanol etc.; Used method is meant the conventional method of Chinese medicine extraction, can be decocting method, reflux extraction, infusion process, percolation or continuous extraction etc.For example, the Radix Astragali can prepare Radix Astragali total saponins or astragalus polysaccharides with the method for water extract-alcohol precipitation, Radix Rhodiolae can prepare Radix Rhodiolae extract with the method for alcohol reflux or water extract-alcohol precipitation, and Rhizoma Smilacis Chinensis can prepare Rhizoma Smilacis Chinensis total saponins with the method for alcohol reflux or water extract-alcohol precipitation.The invention provides the preferred extraction and preparation technique of the Radix Astragali (is main effective ingredient with total saponins or polysaccharide), Radix Rhodiolae (is main effective ingredient with rhodioside), Rhizoma Smilacis Chinensis (is main effective ingredient with total saponins).

The concrete preparation method of crude drug is as follows:

Because Radix Astragali total saponins and astragalus polysaccharides all have activity aspect the brain function improving, and be so " extracting separately " method of the Radix Astragali can adopt different extracting method because of the difference of its active component, as follows respectively:

With total saponins is the preferred extraction and preparation technique of the Radix Astragali of main effective ingredient, as follows:

Get Milkvetch Root, decoct with water three times, each 1.5 hours, add 10 times of amounts of water, two for the first time, be 8 times of amounts for three times, collecting decoction, filter, it is 1.20～1.25 (60 ℃) that filtrate is concentrated into relative density, handles 2 times with ethanol precipitation, containing the alcohol amount in the solution for the first time is 75%, be 85% for the second time, each all cold preservation is placed, and reclaims ethanol and be concentrated into every 1ml to be equivalent to crude drug 10g, be added on the macroporous adsorptive resins of having handled well, earlier with the water of 2 times of volumes towards post, 70% ethanol elution of 4 times of volumes of reuse, collection eluent, concentrating under reduced pressure, vacuum drying, promptly.Radix Astragali total saponins yield by this prepared is 0.5～2%, and the content of total saponins is not less than 50%, and wherein the content of astragaloside is not less than 2.0%.

The Radix Astragali can also extract preparation by following technology, but is not limited only to following technology:

Technology one: get Milkvetch Root, decoct with water three times, each 2 hours, collecting decoction, filter, it is 1.20～1.25 (60 ℃) that filtrate is concentrated into relative density, handles 2 times with ethanol precipitation, containing amount of alcohol in the solution for the first time is 60%, be 85% for the second time, each all cold preservation is placed, and reclaims ethanol and be concentrated into every 1ml to be equivalent to crude drug 10g, concentrating under reduced pressure, vacuum drying, promptly.Radix Astragali total saponins yield by this prepared is 2～4%, and the content of total saponins is not less than 40%, and wherein the content of astragaloside is not less than 1%.

Technology two: get Milkvetch Root, decoct with water three times, each 1.5 hours, collecting decoction filtered, it is 1.20～1.25 (60 ℃) that filtrate is concentrated into relative density, handle to make that to contain amount of alcohol be 60% for 1 time with ethanol precipitation, cold preservation is placed, and reclaims ethanol and be concentrated into every 1ml to be equivalent to crude drug 10g, and concentrating under reduced pressure, vacuum drying, promptly.Radix Astragali total saponins yield by this prepared is 3～5%, total saponin content be not less than 30%, wherein the content of astragaloside is not less than 1%.

With polysaccharide is the preferred extraction and preparation technique of the Radix Astragali of main effective ingredient, as follows:

Get Milkvetch Root, add 7 times of amount 70% ethanol extraction secondaries, each 2 hours, extracting solution discards, the slag extracting in water secondary of getting it filled, merge extractive liquid,, the ratio that is concentrated into extracting liquid volume and raw medicinal herbs is 1.05:1, add ethanol precipitation and make and contain the alcohol amount and reach 70%, filter, must precipitate, precipitation 70% washing with alcohol, the dissolving of reuse suitable quantity of water filters, and filtrate is crossed macroporous resin, the water eluting, collect water lotion, water lotion is concentrated into medicine liquid volume, add ethanol and make and contain alcohol and measure and reach 70% with the medical material ratio is 1:2.5, must precipitate, to precipitate with 95% ethanol and washing with acetone dehydration, drying under reduced pressure (60 ℃), promptly.Astragalus polysaccharides yield by this prepared is 0.5～2%, and the content of polysaccharide is not less than 50%.

Technology one: get Milkvetch Root, add the water reflux, extract, three times, each 2 hours, merge extractive liquid, filters, and it is 1.15～1.23 that filtrate decompression is concentrated into relative density, add ethanol and make and contain alcohol amount and reach 80%, left standstill 24 hours, filter, precipitation is dissolved in water, and filters, and adds ethanol again and makes and contain the alcohol amount and reach 85%, left standstill 24 hours, and filtered collecting precipitation, vacuum drying, promptly.Astragalus polysaccharides yield by this prepared is 2～4%, and the content of polysaccharide is not less than 40%.

Technology two: get Milkvetch Root, add 10 times of amount 80% ethanol extractions 4 hours, extracting solution discards, the slag extracting in water secondary of getting it filled, each 2 hours, add 10 times of amounts of water, merge extractive liquid, at every turn, filter, filtrate adds ethanol to be made and contains alcohol amount and reach 85%, filters, and filtrate decompression is concentrated into the thick paste shape, spray drying, promptly.Astragalus polysaccharides yield by this prepared is 3～4%, and the content of polysaccharide is not less than 35%.

Radix Rhodiolae can extract preparation by following technology, but is not limited only to following technology:

Technology one: get the Radix Rhodiolae medical material, add 70% ethanol extraction three times, add 10 times of amounts for the first time, refluxed 1 hour, and added 8 times of amounts for the second time, refluxed 1 hour, add 8 times of amounts for the third time, refluxed 1 hour, extracting solution filters, filtrate recycling ethanol, and to be evaporated to relative density be 1.05～1.10, adds 2 times of water gagings, stirs evenly, cold preservation is more than 24 hours, filter, it is 1.05～1.10 that filtrate decompression is concentrated into relative density, and concentrated solution is with partly measuring Petroleum ether extraction three times, discard petroleum ether, reuse equivalent n-butanol extraction four times, merge extractive liquid,, reclaim under reduced pressure, vacuum drying or spray drying, promptly.The Radix Rhodiolae extract yield that makes by this technology is 6～～8%, and the total phenol property material is not less than 50%, and wherein rhodioside is not less than 3%.

Technology two; Get the Radix Rhodiolae medical material, add 70% ethanol extraction three times, add 10 times of amounts for the first time, refluxed 1 hour, and added 8 times of amounts for the second time, refluxed 1 hour, add 8 times of amounts for the third time, refluxed 1 hour, extracting solution filters, filtrate recycling ethanol, and to be evaporated to relative density be 1.05～1.10, adds 2 times of water gagings, stir evenly, cold preservation filtered more than 24 hours, it is 1.05～1.10 that filtrate decompression is concentrated into relative density, get concentrated solution, last macroporous resin column or polyamide column, elder generation's water elution of 30 times of amounts of concentrated solution weight, discard eluent, 30 times of amounts of reuse, 80% ethanol elution is collected eluent, reclaim under reduced pressure, vacuum drying or spray drying, promptly.The Radix Rhodiolae extract yield that makes by this technology is 6～8%, and the total phenol property material is not less than 50%, and wherein rhodioside is not less than 3%.

Technology three: get the Radix Rhodiolae medical material, add 60% ethanol extraction three times, add 10 times of amounts for the first time, refluxed 1 hour, and added 8 times of amounts for the second time, refluxed 1 hour, add 8 times of amounts for the third time, refluxed 1 hour, extracting solution filters, filtrate recycling ethanol, and to be evaporated to relative density be 1.05～1.10, adds 2 times of water gagings, stirs evenly, cold preservation is more than 24 hours, filter, it is 1.05～1.10 that filtrate decompression is concentrated into relative density, and adding ethanol, to make ethanol content be 80%, stir evenly, cold preservation filtered decompression filtrate recycling ethanol more than 24 hours, vacuum drying or spray drying, promptly.Perhaps with decompression filtrate recycling ethanol, and to be evaporated to relative density be 1.05～1.10, with equivalent n-butanol extraction four times, merge extractive liquid,, reclaim under reduced pressure, vacuum drying or spray drying, promptly.The Radix Rhodiolae extract yield that makes by this technology is 6～8%, and the total phenol property material is not less than 50%, and wherein rhodioside is not less than 3%.

Technology four: get the Radix Rhodiolae medical material, add 70% ethanol extraction three times, add 10 times of amounts for the first time, refluxed 1 hour, for the second time add 8 times of amounts, refluxed 1 hour, add 8 times of amounts for the third time, refluxed 1 hour, extracting solution filters, filtrate recycling ethanol, and to be evaporated to relative density be 1.05～1.10, add 2 times of water gagings, stir evenly, cold preservation filtered more than 24 hours, it is 1.05～1.10 that filtrate decompression is concentrated into relative density, with equivalent n-butanol extraction four times, merge extractive liquid,, reclaim under reduced pressure, vacuum drying or spray drying, promptly.The Radix Rhodiolae extract yield that makes by this technology is 6～8%, and the total phenol property material is not less than 50%, and wherein rhodioside is not less than 4%.

With total saponins is the preferred extraction and preparation technique of the Rhizoma Smilacis Chinensis of main effective ingredient, as follows:

Get the Rhizoma Smilacis Chinensis medical material, thinly slice, add 70% alcohol reflux three times, each 2 hours, merge extractive liquid, filters, and filtrate recycling ethanol also is concentrated into nothing alcohol flavor, thin up becomes every 1ml to contain crude drug 2g, put coldly, the n-butyl alcohol jolting that adds 1/2 volume is extracted 3 times, merges n-butanol extracting liquid, decompression and solvent recovery, and vacuum drying, get extract powder and add the suitable quantity of water dissolving, be added on the resin column of having handled well, the flushing in 3～4BV/ hour of elder generation's water is to closely colourless, reuse 70% ethanol with 2～3BV/ hour towards post, collect eluent, reclaim ethanol and be concentrated into the thick paste of relative density 1.30～1.35, vacuum drying, promptly.Rhizoma Smilacis Chinensis total saponins yield by this prepared is 1～3%, and the content of Rhizoma Smilacis Chinensis total saponins is not less than 50%.

Rhizoma Smilacis Chinensis also can be extracted preparation by following technology, but is not limited only to following technology:

Technology one: get the Rhizoma Smilacis Chinensis medical material, thinly slice, decoct with water secondary, each 2 hours, collecting decoction filtered, filtrate is concentrated into relative density 1.35～1.40, be added on the resin column of having handled well, flushing in first water 3～4BV/ hour is to closely colourless, reuse 70% ethanol with 2～3BV/ hour towards post, collect eluent, reclaim ethanol and be concentrated into the thick paste of relative density 1.30～1.35, vacuum drying, promptly.Rhizoma Smilacis Chinensis total saponins yield by this prepared is 3～4%, and the content of Rhizoma Smilacis Chinensis total saponins is not less than 30%.

Technology two: get the Rhizoma Smilacis Chinensis medical material, thinly slice, decoct with water secondary, each 2 hours, collecting decoction filtered, filtrate is concentrated into relative density 1.35～1.40, adds ethanol and makes and contain alcohol amount and reach 70%, leaves standstill 24 hours, filter, precipitation is dissolved in water, and filters, add ethanol again and make and contain alcohol amount and reach 80%, left standstill 12 hours, filter, collecting precipitation, vacuum drying, promptly.Rhizoma Smilacis Chinensis total saponins yield by this prepared is 4～6%, and the content of Rhizoma Smilacis Chinensis total saponins is not less than 20%.

Pharmaceutical composition of the present invention, can also replace the Radix Astragali, Radix Rhodiolae extract to replace Radix Rhodiolae, Rhizoma Smilacis Chinensis total saponins to replace Rhizoma Smilacis Chinensis to feed intake by Radix Astragali total saponins or astragalus polysaccharides makes, calculate with respect to the yield of medical material according to extract, pharmaceutical composition of the present invention can have following two kinds of different proportionings, and weight portion is respectively:

Proportioning 1: 2～200 parts of Radix Astragali total saponinss, 6～160 parts of Radix Rhodiolae extracts, 2～90 parts of Rhizoma Smilacis Chinensis total saponinss, be preferably 5～100 parts of Radix Astragali total saponinss, 12～80 parts of Radix Rhodiolae extracts, 3～45 parts of Rhizoma Smilacis Chinensis total saponinss, more preferably 10～40 parts of Radix Astragali total saponinss, 24～32 parts of Radix Rhodiolae extracts, 6～18 parts of Rhizoma Smilacis Chinensis total saponinss.

Proportioning 2: 2～200 parts of astragalus polysaccharidess, 6～160 parts of Radix Rhodiolae extracts, 2～90 parts of Rhizoma Smilacis Chinensis total saponinss, be preferably 5～100 parts of astragalus polysaccharidess, 12～80 parts of Radix Rhodiolae extracts, 3～45 parts of Rhizoma Smilacis Chinensis total saponinss, more preferably 10～40 parts of astragalus polysaccharidess, 24～32 parts of Radix Rhodiolae extracts, 6～18 parts of Rhizoma Smilacis Chinensis total saponinss.

In the aforementioned pharmaceutical compositions, the main effective ingredient of Radix Astragali total saponins is a total saponins, and the content of total saponins is not less than 30%, preferably is not less than 50%, and the content of astragaloside is not less than 1.0%, preferably is not less than 2.0%; The main effective ingredient of astragalus polysaccharides be polysaccharide, the content of polysaccharide is not less than 35%, preferably is not less than 50%; The main effective ingredient of Radix Rhodiolae extract is the total phenol property material, and the content of total phenol property material is not less than 50%, and wherein the content of rhodioside is not less than 3%; The main effective ingredient of Rhizoma Smilacis Chinensis total saponins is a total saponins, and the content of total saponins is not less than 20%, preferably is not less than 50%.

Pharmaceutical composition of the present invention, the consumption of drug component is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.Above-mentioned composition as if being unit with the gram, can be made the preparation of 10～1000 consumptions, as liquid drugs injection or powder pin, can be made into 10～2000,1～10 of each consumption.As tablet or capsule, can be made into 10～2000, take 1～10 at every turn.Above-mentioned composition is by weight as proportioning, can be unit with kilogram or ton as large-scale production, and small-scale production can be unit with the gram also.Above-mentioned parts by weight are for especial patient, and the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.

Pharmaceutical composition of the present invention is mainly used in the medicine that preparation improves brain function.Pharmacological effect studies show that, pharmaceutical composition of the present invention can significantly improve the ability of learning and memory that scopolamine is caused amnemonic mice, normal mouse, alzheimer disease rat, vascular dementia rats, significantly improves the normal pressure hypoxia-bearing capability of mice; Can be used for improving ability of learning and memory, protection cerebral ischemia or anoxia-induced apoptosis, treatment alzheimer disease, vascular dementia etc.

Pharmaceutical composition of the present invention can be made clinically arbitrary or pharmaceutically acceptable dosage form, and optimizing injection and oral formulations can be applied to the patient who needs this treatment in the mode of oral or parenteral.

When being used for parenteral, can be made into injection.Injection means the intravital solution of confession injection, emulsion or the suspension that medicine is made and supplies to face with preceding preparation or be diluted to solution or the sterile preparation of the powder of suspension or concentrated solution that injection can be divided into injection, injectable sterile powder and concentrated solution for injection.Injection means that the confession that medicine is made is injected into sterile solution type injection, emulsion-type injection or the suspension type injection of using in the body, can be used for intramuscular injection, intravenous injection, intravenous drip etc.; Its specification has 1ml, 2ml, 5ml, 10ml, 20ml, 50ml, 100ml, 200ml, 250ml, 500ml etc., and wherein large volume (generally the being not less than 100ml) injection of using for intravenous drip also claims venous transfusion.Injectable sterile powder means that confession that medicine is made is faced with the suitable sterile solution of preceding usefulness and is mixed with settled solution or the evenly sterilized powder or the aseptic block of suspension, available suitable solvent for injection preparation back injection, also available venous transfusion preparation posterior vein instils; Sterilized powder makes with solvent crystallization, spray drying method or freeze-drying etc.Concentrated solution for injection means that confession that medicine is made faces the aseptic concentrated solution of using for intravenous drip with preceding dilution.

Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, pill, granule etc.; Also can be made into oral liquid, as oral solution, oral suspensions, syrup etc.Tablet means disk shape or the special-shaped flaky solid preparation that medicine and the auxiliary materials and mixing compacting that suits form, based on oral ordinary tablet, other has buccal tablet, Sublingual tablet, mouth paster, chewable tablet, dispersible tablet, fuse, effervescent tablet, slow releasing tablet, controlled release tablet and enteric coatel tablets etc.Capsule means medicine or is added with the adjuvant filling in Capsules or be sealed in solid preparation in the soft capsule material, according to its dissolving and release characteristics, can be divided into hard capsule (being commonly referred to as capsule), soft capsule (soft gelatin capsule), slow releasing capsule, controlled release capsule and enteric coated capsule etc.Pill means medicine and suitable adjuvant uniform mixing, and the spherical or near-spherical solid preparation so that proper method is made comprises drop pill, sugar pill, piller etc.Granule means that medicine and suitable adjuvant make the dried particles shape preparation with certain particle size, can be divided into soluble particles (being commonly referred to as granule), mix suspension grain, effervescent granule, enteric coated particles, slow-releasing granules and controlled release granule etc.Oral solution means that medicine dissolution makes for oral supernatant liquid preparation in suitable solvent.Oral suspensions means the slightly solubility solid drugs, is dispersed in the liquid medium, makes for oral suspension body preparation, also comprises dry suspension or dense suspension.Syrup means the dense aqueous sucrose solution that contains medicine.

The preparation of aforementioned pharmaceutical compositions, can adopt the conventional method production in the existing pharmaceutical field, various acceptable accessories be can add in case of necessity, diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc. comprised.

When making injection, can adopt the conventional method production in the existing pharmaceutical field, optional use solvent or non-aqueous solvent.The most frequently used aqueous solvent is a water for injection, also available 0.9% sodium chloride solution or other suitable aqueous solutions; Non-aqueous solvent commonly used is a vegetable oil, is mainly the injection soybean oil, and other also have the aqueous solution of ethanol, propylene glycol, Polyethylene Glycol etc.During the preparation injection, can not add additives, also can add suitable additives, as osmotic pressure regulator, pH value regulator, solubilizing agent, filler, antioxidant, antibacterial, emulsifying agent, suspending agent etc. according to the character of medicine.Osmotic pressure regulator commonly used comprises sodium chloride, glucose, potassium chloride, magnesium chloride, calcium chloride, sorbitol etc., preferred sodium chloride or glucose; PH value regulator commonly used comprises acetic acid-sodium acetate, lactic acid, citric acid-sodium citrate, sodium bicarbonate sodium carbonate etc.; Solubilizing agent commonly used comprises polyoxyethylene sorbitan monoleate, propylene glycol, lecithin, polyoxyethylene castor oil etc.; Filler commonly used comprises lactose, mannitol, sorbitol, dextran etc.; Antioxidant commonly used has sodium sulfite, sodium sulfite, sodium pyrosulfite etc.; Antibacterial commonly used is phenol, cresol, chlorobutanol etc.Injection container commonly used has glass ampule, vial, plastic ampoule, plastic bottle etc.

When making oral formulations, can add suitable filler, binding agent, disintegrating agent, lubricant etc.Filler commonly used comprises starch, Icing Sugar, calcium phosphate, calcium sulfate two water things, dextrin, microcrystalline Cellulose, lactose, pregelatinized Starch, mannitol etc.: typical binders comprises sodium carboxymethyl cellulose, PVP-K30, hydroxypropyl cellulose, starch slurry, methylcellulose, ethyl cellulose, hypromellose, gelling starch etc.; Disintegrating agent commonly used comprises dried starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose etc.; Conventional lubricants comprises magnesium stearate, Pulvis Talci, sodium lauryl sulphate, micropowder silica gel etc.

Pharmaceutical composition of the present invention has following advantage:

(1) provides a kind of new compound recipe to improve the medicine of brain function, met clinical needs.

(2) consumption to pharmaceutical composition Chinese medicine component of the present invention has carried out groping in a large number research, by pharmaceutical composition of the present invention scopolamine is caused the research of the influence of amnemonic mice and normal mouse learning and memory, filter out weight proportion with significant curative effect.

(3) pharmacological effect studies show that, pharmaceutical composition of the present invention can significantly reduce the frequency of training that AD rat Y-maze experiment reaches association's standard, significantly reduces the cerebral cortex lipofuscin content; Significantly reduce the frequency of training that VD rat Y-maze experiment reaches association's standard, what the disposable passive avoidance of significant prolongation was tested steps into incubation period; Significantly improve the normal pressure hypoxia-bearing capability of mice, the time-to-live under the significant prolongation mice normobaric hypoxia state; And the effect of pharmaceutical composition of the present invention is better than the Radix Astragali or its extract, Radix Rhodiolae or its extract, Rhizoma Smilacis Chinensis or the individually dosed effect of its extract, has the effect of Synergistic, has produced beyond thought effect.

(4) pharmaceutical composition of the present invention can feed intake with the Radix Astragali, Radix Rhodiolae, Rhizoma Smilacis Chinensis, can be raw material with Radix Astragali extract, Radix Rhodiolae extract, Rhizoma Smilacis Chinensis total saponins also, can be made into clinically arbitrary or pharmaceutically acceptable dosage form.

(5) preparation that pharmaceutical composition of the present invention is made or used extract have carried out discriminating, assay, stability study etc., and effective ingredient is clear and definite, content is high, and better stability of preparation is convenient to control product quality, guarantee clinical drug safety.

(6) provide preferable preparation technique, simple and easy to do, and quality of the pharmaceutical preparations height, be adapted to industrialized great production.

Below routine by experiment beneficial effect of further setting forth pharmaceutical composition of the present invention, these experimental examples comprise the pharmacodynamic experiment and the stability experiment of pharmaceutical composition of the present invention.Pharmaceutical composition of the present invention has following beneficial effect, but this should be interpreted as that pharmaceutical composition of the present invention only has following beneficial effect.

Replacing with Radix Astragali total saponins, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins with HHB1 in the following experimental example is the pharmaceutical composition of main effective ingredient, and replacing with astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins with HHB2 is the pharmaceutical composition of main effective ingredient.Radix Astragali total saponins used in the following experimental example is Embodiment 1The preparation gained, used astragalus polysaccharides is Embodiment 2The preparation gained, used Radix Rhodiolae extract is Embodiment 3The preparation gained, used Rhizoma Smilacis Chinensis extract is Embodiment 4The preparation gained.

Experimental example 1 pharmaceutical composition of the present invention influences learning and memory of little mouse

The animal subject healthy mice, 320, body weight 20～25g, male, be divided into 32 groups at random, 10 every group.

Test sample normal saline: commercial

The Radix Astragali total saponins sheet: self-control is equivalent to crude drug 10g

The astragalus polysaccharides sheet: self-control is equivalent to crude drug 10g

The Radix Rhodiolae sheet: self-control is equivalent to crude drug 2g

The Rhizoma Smilacis Chinensis sheet: self-control is equivalent to crude drug 3g

(Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 1: self-control sees Table 1-1 (is main effective ingredient with Radix Astragali total saponins, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins)

(Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 2: self-control sees Table 1-1 (is main effective ingredient with astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins)

Table 1-1 pharmaceutical composition of the present invention to scopolamine cause memory acquisition disturbance model mice learning and memory influence (X ± S, n=10)

Compare with model group; ^*P＜0.05, ^*P＜0.01;

Compare with Radix Astragali total saponins injection group: ^aP＜0.05, ^bP＜0.01; Compare with the astragalin injection group: ^cP＜0.05, ^dP＜0.01;

Compare with the gadol injection group: ^eP＜0.05, ^fP＜0.01; Compare with Rhizoma Smilacis Chinensis injection group: ^gP＜0.05, ^hP＜0.01.

The experimental technique mice is divided into 32 groups at random, 10 every group, is respectively matched group, model group and each administration group.Scopolamine is caused the influence of memory acquisition disturbance: each administration group is by table 1-1 gastric infusion (dosage is by crude drug), and matched group and model group award the equivalent normal saline, administration 30d, once a day.Administration 29d adopts diving tower method, darkness avoidance test to train, every group of lumbar injection scopolamine of 20min 1mg/kg before the training, matched group and model group injecting normal saline.Test length incubation period behind the 24h is as the memory index.

Experimental result and conclusion The results see Table 1-1.Compare with matched group, Radix Astragali total saponins sheet, astragalus polysaccharides sheet, Radix Rhodiolae sheet and Rhizoma Smilacis Chinensis sheet can significantly improve learning and memory abilities in aging mice (p＜0.05); 2 of 1 of (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) that the Radix Astragali 4～100g, Radix Rhodiolae 1～20g, Rhizoma Smilacis Chinensis 1.5～30g make and (Radix Astragali+Radix Rhodiolaes+Rhizoma Smilacis Chinensis) can be significantly or the utmost point significantly improve learning and memory abilities in aging mice (p＜0.05, p＜0.01), the effect of the sheet made of the Radix Astragali 10～50g, Radix Rhodiolae 2～10g, Rhizoma Smilacis Chinensis 3～15g is better.The effect of pharmaceutical composition of the present invention is better than single effect with the Radix Astragali, Radix Rhodiolae or Rhizoma Smilacis Chinensis, points out pharmaceutical composition of the present invention to have the collaborative effect that medicine causes the brain function of memory acquisition disturbance mice that improves.

Experimental example 2 pharmaceutical compositions of the present invention are to the influence of normal learning and memory of little mouse

The animal subject healthy mice, 270, body weight 20～25g, the male and female dual-purpose is divided into 27 groups at random, 10 every group.

Test sample sodium chloride injection (matched group): 250ml:2.25g, Shangdong Changfu Jiejing Pharmaceutical Industry Co., Ltd.

The Radix Astragali total saponins injection: self-control is equivalent to crude drug 10g

Astragalin injection: self-control is equivalent to crude drug 10g

Gadol injection: self-control is equivalent to crude drug 2g

The Rhizoma Smilacis Chinensis injection: self-control is equivalent to crude drug 3g

(Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 1 injection: self-control sees Table 1-2 (is main effective ingredient with Radix Astragali total saponins, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins)

(Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 2 injection: self-control sees Table 1-2 (is main effective ingredient with astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins)

The experimental technique mice is divided into 27 groups at random, 10 every group, is respectively matched group and each administration group.The matched group lumbar injection gives sodium chloride injection, is subjected to the reagent thing to be diluted to the desired concn intraperitoneal injection by dosage shown in the table 1-2 with sodium chloride injection, once a day, and successive administration 30 days.Carry out the normal mouse water maze laboratory: for the first time (A) begins training to mice from nearby, prolongs (from B) for the second time and begins to train, and trains continuously 3 times, can reach home to 80% above animal; Last, training from the off.Calculate the errors number of each treated animal and the time of reaching home.

Experimental result and conclusion The results see Table 1-2.Compare with matched group, each administration group mice is in water maze laboratory, and time of on average reaching home and errors number all are lower than matched group.Radix Astragali total saponins injection, astragalin injection, gadol injection and Rhizoma Smilacis Chinensis injection can significantly improve learning and memory abilities in aging mice (p＜0.05); (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 1 injection that the Radix Astragali 4～100g, Radix Rhodiolae 1～20g, Rhizoma Smilacis Chinensis 1.5～30g make and (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 2 injection to can be significantly or the utmost point significantly improve learning and memory abilities in aging mice (p＜0.05, p＜0.01), the effect of the injection made of the Radix Astragali 10～50g, Radix Rhodiolae 2～10g, Rhizoma Smilacis Chinensis 3～15g is better.

Table 1-2 pharmaceutical composition of the present invention to the influence of normal learning and memory of little mouse (X ± S, n=10)

Compare with matched group: ^*P＜0.05, ^*P＜0.01;

Compare with Radix Astragali total saponins injection group: ^aP＜0.05, ^bP＜0.01: compare with the astragalin injection group: ^cP＜0.05, ^dP＜0.01;

Compare with Radix Astragali total saponins injection group, (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 1 injection of each proportioning can significantly improve learning and memory abilities in aging mice (p＜0.05).Compare with the astragalin injection group, (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 2 injection of each proportioning can significantly improve learning and memory abilities in aging mice (p＜0.05).Compare with gadol injection, (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 1 injection of each proportioning and (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 2 injection can significantly improve learning and memory abilities in aging mice (p＜0.05).Compare with the Rhizoma Smilacis Chinensis injection, (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 1 injection of each proportioning and (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 2 injection can significantly improve learning and memory abilities in aging mice (p＜0.05).

Experimental result shows, pharmaceutical composition of the present invention can significantly improve the ability of learning and memory of normal mouse, and, under the identical dosage, (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 1 injection of each proportioning and the effect of (Radix Astragali+Radix Rhodiolae+Rhizoma Smilacis Chinensis) 2 injection all are better than the effect that Radix Astragali total saponins injection, astragalin injection, gadol injection and Rhizoma Smilacis Chinensis injection use separately.Prompting, the Radix Astragali, Radix Rhodiolae, Rhizoma Smilacis Chinensis have the collaborative effect that improves ability of learning and memory.

Experimental example 3 pharmaceutical compositions of the present invention are to the protective effect of neonate rat cerebral anoxia ischemical reperfusion injury

Animal subject 7 age in days neonate rats, body weight 180～200g, male and female dual-purpose.

Test sample normal saline: commercial

The Radix Astragali total saponins capsule: self-control is equivalent to crude drug 10g

The astragalus polysaccharides capsule: self-control is equivalent to crude drug 10g

Rhodiola rosea capsules: self-control is equivalent to crude drug 2g

The Rhizoma Smilacis Chinensis capsule: self-control is equivalent to crude drug 3g

The HHB1 capsule: self-control is equivalent to Radix Astragali 10g, Radix Rhodiolae 2g, Rhizoma Smilacis Chinensis 3g (is main effective ingredient with Radix Astragali total saponins, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins)

The HHB2 capsule: self-control is equivalent to Radix Astragali 10g, Radix Rhodiolae 2g, Rhizoma Smilacis Chinensis 3g (is main effective ingredient with astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins)

The experimental technique mice is divided into 13 groups at random, 10 every group, is respectively matched group, sham operated rats, cerebral anoxia ischemia-reperfusion group (HIR) and each administration group.The preparation of cerebral anoxia ischemia-reperfusion injury model: 7 age in days newborn rats are lain on the back and are fixed on the operation plate, ethanol partly sterilised, separate bilateral common carotid arteries, using miniature vascular clamp folder closes bilateral common carotid arteries 1h, places 37 ℃ of constant temperature simultaneously, contains anoxia 2h in the anoxia case of 8% oxygen.With 6/0 silk suture cervical incision, return female Mus and continue at one's side to feed after the Hypoxia and ischemia until execution.Sham operated rats is sewed up cervical incision after isolating bilateral common carotid arteries immediately, and the normal control group will not any processing.Medication: be diluted to desired concn for the reagent thing with normal saline, immediately by dosage gastric infusion shown in the table 1-3, same dose repeats gastric infusion behind the 24h behind the neonate rat cerebral anoxia ischemia.Normal control group, sham operated rats and HIR group are irritated stomach and are given isopyknic normal saline.Sample preparations: broken end was got brain after each organized cerebral anoxia ischemia-reperfusion 48h, and cerebral tissue places 10% neutral formalin to fix 2～3d.Through routine dehydration, after the paraffin embedding, get be equivalent to biauricular line before the 2mm level do crown position brain tissue slice, thick 4 microns of sheet, HE dyeing, microscopically is to be checked.According to the form below calculates the scoring of Hypoxia and ischemia neonate rat encephalopathy reason.

Hypoxia and ischemia neonate rat encephalopathy reason standards of grading

Behind experimental result and the conclusion cerebral anoxia ischemia-reperfusion 48h, the pathology assessment total points of normal control group and sham operated rats rat is 1, and cerebral tissue is normal, no abnormal variation.The brain tissue impairment of HIR group rat is serious, pathology assessment total points average out to 35.21.Compare with HIR group, the brain tissue impairment of each administration group rat all significantly or extremely shows and alleviates, pathology assessment total points all significantly or extremely significantly descend (p＜0.05, p＜0.01).Compare with the Radix Astragali, Radix Rhodiolae or Rhizoma Smilacis Chinensis group with single, the better effects if of each dosage group of pharmaceutical composition group of the present invention, prompting, the Radix Astragali, Radix Rhodiolae, Rhizoma Smilacis Chinensis have the effect of collaborative anti-cerebral ischemia anoxia reperfusion injury.

The table 1-3 respectively organize brain tissue slice pathology assessment (X ± S, n=10)

Compare with matched group: ^#P＜0.05; Compare with model group: ^*P＜0.05, ^*P＜0.01;

Compare with Radix Astragali total saponins injection group; ^aP＜0.05, ^bP＜0.01; Compare with the astragalin injection group: ^cP＜0.05, ^dP＜0.01;

Experimental example 4 pharmaceutical compositions of the present invention are to the effect of experimental alzheimer disease (AD) rat

The animal subject healthy rat, 120, body weight 180～200g, the male and female dual-purpose is divided into 12 groups at random, 10 every group.

The Radix Astragali total saponins injection: self-control, 2ml contains Radix Astragali total saponins 130mg (being equivalent to crude drug 10g)

Astragalin injection: self-control, 2ml contains astragalus polysaccharides 128mg (being equivalent to crude drug 10g)

Gadol injection: self-control, 2ml contains Radix Rhodiolae total phenols material 146mg (being equivalent to crude drug 2g)

The Rhizoma Smilacis Chinensis injection: self-control, 2ml contains Rhizoma Smilacis Chinensis total saponins 61mg (being equivalent to crude drug 3g)

The HHB1 injection: self-control, 5ml:337mg contains Radix Astragali total saponins 130mg (being equivalent to crude drug 10g), Radix Rhodiolae extract 156mg (being equivalent to crude drug 2g), Rhizoma Smilacis Chinensis total saponins 61mg (being equivalent to crude drug 3g)

The HHB2 injection: self-control, 5ml:335mg contains astragalus polysaccharides 128mg (being equivalent to crude drug 10g), Radix Rhodiolae extract 146mg (being equivalent to crude drug 2g), Rhizoma Smilacis Chinensis total saponins 61mg (being equivalent to crude drug 3g)

The experimental technique rat is divided into 12 groups at random, 10 every group, is respectively matched group, model group and each administration group.Control rats lumbar injection sodium chloride injection 1ml, every day 1 time, continuous 6 weeks.Model group rats by intraperitoneal injection galactose 50mg/kg, every day 1 time, continuous 6 weeks.Each administration group rats by intraperitoneal injection galactose 50mg/kg, every day 1 time, continuous 6 weeks; Begin intraperitoneal injection the 2nd weekend, continuous 4 weeks by table 1-4.Carry out rat Y-type maze experiment, the counting rat reaches the frequency of training of association's standard.Get the rat cerebral cortex tissue, measure the content of cortex lipofuscin (Lipofuscin).

Experimental result and conclusion The results see Table 1-4.Compare with matched group, the frequency of training that model group rat Y-type maze experiment reaches association's standard significantly raises (p＜0.05), and the cerebral cortex lipofuscin content significantly raises (p＜0.05), and alzheimer disease (AD) rat modeling success is described.Compare with model group, each administration group all reduces the frequency of training that the AD rat reaches association's standard, reduces the cerebral cortex lipofuscin content.Radix Astragali total saponins injection, astragalin injection all reduce the frequency of training that the AD rat reaches association's standard, reduce the cerebral cortex lipofuscin content, but there was no significant difference.Gadol injection significantly reduces the frequency of training (p＜0.01) that the AD rat reaches association's standard, significantly reduces cerebral cortex lipofuscin content (p＜0.01); The Rhizoma Smilacis Chinensis injection significantly reduces the frequency of training (p＜0.05) that the AD rat reaches association's standard, significantly reduces cerebral cortex lipofuscin content (p＜0.05); Each dosage HHB1 injection and HHB2 injection all extremely significantly reduce the frequency of training (p＜0.01) that the AD rat reaches association's standard, extremely significantly reduce cerebral cortex lipofuscin content (p＜0.01).

Table 1-4 pharmaceutical composition of the present invention to the influence of AD rat model (X ± S, n=10)

Experimental result shows that pharmaceutical composition of the present invention can significantly reduce the frequency of training that AD rat Y-type maze experiment reaches association's standard, significantly reduce the cerebral cortex lipofuscin content, and effect is relevant with dosage, and the effect of high dose group is best.The effect of each dosage HHB1 injection all is better than the effect that Radix Astragali total saponins injection, gadol injection and Rhizoma Smilacis Chinensis injection use separately, and the effect of each dosage HHB2 injection all is better than the effect that astragalin injection, gadol injection and Rhizoma Smilacis Chinensis injection use separately.Prompting, Radix Astragali total saponins or astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins have the effect of the ability of learning and memory of the collaborative AD of raising rat.

Experimental example 5 pharmaceutical compositions of the present invention are to the effect of vascular dementia (VD) rat

The animal subject healthy rat, body weight 180～200g, male and female dual-purpose.

Test sample sodium chloride injection: 250ml:2.25g, Shangdong Changfu Jiejing Pharmaceutical Industry Co., Ltd.

The Radix Astragali total saponins injection; Self-control, 2ml contains Radix Astragali total saponins 130mg (being equivalent to crude drug 10g)

The HHB1 injection: self-control, 5ml:337mg contains Radix Astragali total saponins 130mg (being equivalent to crude drug 10g), Radix Rhodiolae extract 146mg (being equivalent to crude drug 2g), Rhizoma Smilacis Chinensis total saponins 61mg (being equivalent to crude drug 3g)

Experimental technique VD rat model is with 10% chloral hydrate (350mg/kg) intraperitoneal anesthesia, lie prostrate and be fixed in stereotactic apparatus, row dorsal part neck median incision, expose atlas transverse process wing aperture, coagulate pin with the electricity of diameter 0.5mm and burn the interior vertebral artery of double side wings aperture, cause the permanent occlusion, it is fixing to lie on the back again, row veutro neck median incision separates bilateral common carotid arteries, and " 4 " number silk thread threading is standby.Etherization behind the 24h closes bilateral common carotid arteries 5min with arteriole folder folder, and folder closes 3 times altogether, each 1h at interval.Local wound is handled with gentamycin, sews up conventional breeding observing then.The sham operated rats treatment step is the same, does not burn with common carotid artery folder and closes but do not carry out vertebral artery.Postoperative 5 days, the modeling rat is kept away dark experiment, and errors number in the record 5min clock surpasses 5 persons, and there are disturbances of intelligence such as Learning and Memory is bad in prompting, includes the object of observation in, to the bad animal of Learning and Memory not occurring, is then rejected.110 of the rats of the modeling success of choosing are divided into 11 groups at random, 10 every group, are respectively model group and each administration group.Sham operated rats and model group lumbar injection sodium chloride injection 1ml, each administration group rat is by table 1-5 intraperitoneal injection, every day 1 time, continuous 4 weeks.Carry out rat Y-type maze experiment, counting rat Y-type labyrinth reaches the frequency of training of association's standard.Carry out the experiment of disposable passive avoidance: a 40w electric filament lamp is suspended from 40cm place, pedal top, rat is placed on the pedal tail door opening is write down it enters before the camera bellows time of staying on pedal, promptly go on foot people's incubation period, test and in for three days on end, finish.

Table 1-5 pharmaceutical composition of the present invention to the influence of VD rat (X ± S, n=10)

Compare with matched group: ^#P＜0.05, ^##P＜0.01; Compare with model group: ^*P＜0.05, ^*P＜0.01;

Experimental result and conclusion experimental result see Table 1-5.Compare with sham operated rats, the frequency of training that model group rat Y-type maze experiment reaches association's standard extremely significantly raise (p＜0.05), extremely significantly shorten (p＜0.01) incubation period of stepping into of disposable passive avoidance experiment, and vascular dementia (VD) rat modeling success is described.Compare with model group, each administration group all reduces the frequency of training that VD rat Y-type maze experiment reaches association's standard, prolongs stepping into incubation period of disposable passive avoidance experiment.The Radix Astragali total saponins injection significantly reduces the frequency of training (p＜0.05) that VD rat Y-type maze experiment reaches association's standard, the stepping into incubation period of the disposable passive avoidance of significant prolongation experiment (p＜0.05); Gadol injection significantly reduces the frequency of training (p＜0.01) that VD rat Y-type maze experiment reaches association's standard, the stepping into incubation period of the disposable passive avoidance of significant prolongation experiment (p＜0.01); Astragalin injection, Rhizoma Smilacis Chinensis injection all reduce the frequency of training that VD rat Y-type maze experiment reaches association's standard, prolong stepping into incubation period of disposable passive avoidance experiment, but there was no significant difference; Each dosage HHB1 injection and HHB2 injection all extremely significantly reduce the frequency of training (p＜0.01) that VD rat Y-type maze experiment reaches association's standard, the stepping into incubation period of the disposable passive avoidance of utmost point significant prolongation experiment (p＜0.01).

Experimental result shows that pharmaceutical composition of the present invention can significantly reduce the frequency of training that the VD rat reaches association's standard, and what the disposable passive avoidance of significant prolongation was tested steps into incubation period, and effect is relevant with dosage, and the effect of high dose group is best.And the effect of each dosage group of pharmaceutical composition of the present invention all is better than the effect that Radix Astragali total saponins injection, astragalin injection, gadol injection and Rhizoma Smilacis Chinensis injection use separately.Prompting, Radix Astragali total saponins or astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins have the effect of the ability of learning and memory of the collaborative VD of raising rat.

Experimental example 6 pharmaceutical compositions of the present invention are to the influence of mice normal pressure anoxia enduring

The animal subject healthy mice, 100, body weight 20～25g, the male and female dual-purpose is divided into 10 groups at random, 10 every group.

The Radix Rhodiolae extract injection: self-control, 2ml contains Radix Rhodiolae total phenols material 146mg (being equivalent to crude drug 2g)

The experimental technique mice is divided into 10 groups at random, 10 every group, is respectively matched group and each administration group.Each organizes mice by table 1-6 intraperitoneal injection, every day 1 time, continuous 7 days.Behind the last administration 1h, place the wide mouthed bottle of demarcating 125ml through capacity respectively, the built-in 10g sodica calx of bottle is to absorb CO ₂And moisture content, bottle cap is coated with the vaseline sealing, the death time of record mice.

Experimental result and conclusion The results see Table 1-6.Compare with matched group, each administration group all can prolong the time-to-live of mice.The time-to-live (p＜0.05) of Radix Astragali total saponins injection, astragalin injection, Rhizoma Smilacis Chinensis injection significant prolongation mice, the time-to-live (p＜0.01) of gadol injection utmost point significant prolongation mice, the time-to-live (p＜0.01) of each dosage group HHB1 injection and HHB2 injection utmost point significant prolongation mice.

Experimental result shows, but the time-to-live of pharmaceutical composition significant prolongation mice of the present invention, and effect is relevant with dosage, and the effect of high dose group is best.And the effect of pharmaceutical composition group of the present invention all is better than the effect that Radix Astragali total saponins injection, astragalin injection and gadol injection use separately.Prompting, Radix Astragali total saponins or astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins have the effect of coordinating protection cerebral anoxia damage.

Table 1-6 pharmaceutical composition of the present invention to the effect of mice normal pressure anoxia enduring (X ± S, n=10)

Compare with matched group: ^*P＜0.05, ^*P＜0.01;

Experimental example 7 HHB1 injection, HHB2 injection stability experiment

Test sample hHB1 injection: self-control, 5ml:337mg contains Radix Astragali total saponins 130mg (being equivalent to crude drug 10g), Radix Rhodiolae extract 146mg (being equivalent to crude drug 2g), Rhizoma Smilacis Chinensis total saponins 61mg (being equivalent to crude drug 3g)

Investigation project character, pH value, clarity, related substance, sign content.

Long-term experiment is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and was placed 12 months.Respectively at 3rd month, 6 months, 9 months, 12 months, relatively after the outward appearance, test every index, with result and comparison in 0 month; Increase aseptic and pyrogen test 12 the end of month.

Placed 12 months under the condition of 25 ℃ ± 2 ℃ of experimental result temperature, relative humidity 60% ± 10%, every index has no significant change; At 12 the end of month of long-term experiment, pyrogen, sterility test are all up to specification.

Conclusion is above-mentioned investigation result show, every index of HHB1 injection, HHB2 injection is all more stable, can long term storage, be adapted to that industry is big produces.

4, the specific embodiment

The specific embodiment of form is described in further detail foregoing of the present invention by the following examples, but this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.

Replacing with Radix Astragali total saponins, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins with HHB1 in following examples is the pharmaceutical composition of main effective ingredient, and replacing with astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins with HHB2 is the pharmaceutical composition of main effective ingredient. EmbodimentIn used Radix Astragali total saponins be Embodiment 1The preparation gained, used astragalus polysaccharides is Embodiment 2The preparation gained, used Radix Rhodiolae extract is Embodiment 3The preparation gained, used Rhizoma Smilacis Chinensis total saponins is Embodiment 4The preparation gained.

The preparation of embodiment 1 Radix Astragali total saponins and discriminating and assay

The preparation of Radix Astragali total saponins

Get Milkvetch Root 50kg, decoct with water three times, each 1.5 hours, add 10 times of amounts of water, two for the first time, be 8 times of amounts for three times, collecting decoction, filter, it is 1.20～1.25 (60 ℃) that filtrate is concentrated into relative density, handles 2 times with ethanol precipitation, containing the alcohol amount in the solution for the first time is 75%, be 85% for the second time, each all cold preservation is placed, and reclaims ethanol and be concentrated into every 1ml to be equivalent to crude drug 10g, be added on the macroporous adsorptive resins of having handled well, earlier with the water of 2 times of volumes towards post, 70% ethanol elution of 4 times of volumes of reuse, collection eluent, concentrating under reduced pressure, vacuum drying, promptly.

Prepare three batches of Radix Astragali total saponinss respectively, extract yield sees Table 2-1.

The discriminating of Radix Astragali total saponins

Identification experiment one is got this product 10mg, adds methanol 20ml, reflux 1 hour, filter, filtrate is added on neutral alumina post (100～120 orders, 5g, on the internal diameter 10～15mm), with 40% methanol 100ml eluting, collect eluent, evaporate to dryness, residue adds water 30ml makes dissolving, extract 2 times with water saturated n-butyl alcohol jolting, each 20ml merges n-butyl alcohol liquid; Wash each 20ml with water 2 times; Discard water liquid, n-butyl alcohol liquid evaporate to dryness, residue add methanol 0.5ml makes dissolving, as need testing solution.Other gets the astragaloside reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Drawing each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with lower floor's solution of chloroform-methanol-water (13:7:2), launches, and takes out, and dries, and spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 105 ℃.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, daylight shows down identical sepia speckle, ultra-violet lamp (365nm) shows identical orange-yellow fluorescence speckle down.

Identification experiment two is got this product 10mg, adds ethanol 30ml, reflux 20 minutes, filter, filtrate adds 0.3% sodium hydroxide solution 15ml makes dissolving, filters, and filtrate is regulated pH value to 5～6 with dilute hydrochloric acid, extract with ethyl acetate 15ml jolting, divide and get acetic acid ethyl fluid, filter the filtrate evaporate to dryness with the filter paper that is covered with anhydrous sodium sulfate, residue adds ethyl acetate 1ml makes dissolving, as need testing solution.Other gets Radix Astragali control medicinal material 2g, shines medical material solution in pairs with legal system.Draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, as developing solvent, launch, take out, dry, put in the ammonia steam and inspect under the smoked rearmounted ultra-violet lamp (365nm) with chloroform-methanol (10:1).In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence principal spot of same color.

Respectively above-mentioned three batches of Radix Astragali total saponinss are carried out identification experiment, the result all meets the requirements.

The assay of Radix Astragali total saponins

The assay of total saponins

The preparation precision of reference substance solution takes by weighing the astragaloside reference substance 10mg that is dried to constant weight in 105 ℃, puts in the 100ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, and promptly gets (every 1ml contains astragaloside dry product 0.1mg).

This product 100mg is got in the preparation of need testing solution, and accurate the title decides, and adds water 25ml and makes dissolving, move in the separatory funnel, extract 4 times, each 20ml with water saturated n-butyl alcohol jolting, merge n-butyl alcohol liquid, with the saturated water washing twice of n-butyl alcohol, each 10ml, discard water liquid, n-butyl alcohol evaporate to dryness to the water-bath, residue adds dissolve with methanol, move in the 25ml measuring bottle, and add methanol and be diluted to scale, shake up, filter, get subsequent filtrate, promptly.

The algoscopy precision is measured reference substance solution, each 1ml of need testing solution, puts the 25ml nessler colorimetric tube, puts evaporate to dryness in the water-bath, put coldly, add freshly prepared 5% vanillin-glacial acetic acid solution 0.4ml, perchloric acid 1.6ml, shake up, placed 5 minutes, and put in the boiling water bath and developed the color 15 minutes, take out, put immediately and be cooled to room temperature in the ice bath, add the 8ml glacial acetic acid, shake up, measure absorbance at 538nm wavelength place, calculate, promptly.

The assay of astragaloside

Chromatographic condition and system suitability experiment are filler with the octadecyl silane; With acetonitrile-water (32:68) is mobile phase; Evaporative light scattering detector.Number of theoretical plate calculates with the astragaloside peak and is not less than 4000.

It is an amount of that the preparation precision of reference substance solution takes by weighing the astragaloside reference substance, adds methanol and make the solution that every 1ml contains 0.5mg, promptly.

The preparation precision of need testing solution takes by weighing this product 40mg, and accurate the title decides, and puts in the apparatus,Soxhlet's, add methanol 40ml, merceration spends the night, and it is an amount of to add methanol again, reflux 4 hours, extracting solution reclaim solvent and are concentrated into driedly, and residue adds water 10ml, slight fever makes dissolving, extracts 4 times with water saturated n-butyl alcohol jolting, each 40ml, merge n-butyl alcohol liquid, use ammonia solution thorough washing 2 times, each 40ml, discard ammoniacal liquor, n-butyl alcohol liquid steams thousand, and residue adds water 5ml makes dissolving, put cold, by D101 type macroporous adsorptive resins (internal diameter 1.5cm, long 12cm), with water 50ml eluting, discard water liquid, reuse 40% ethanol 30ml eluting, discard eluent, continue with 70% ethanol 80ml eluting, collect eluent, evaporate to dryness, with dissolve with methanol and be transferred in the 5ml measuring bottle, add methanol and be diluted to scale, shake up, promptly.

Accurate respectively reference substance solution 10 μ l, 20 μ l and the need testing solution 20 μ l of drawing of algoscopy inject chromatograph of liquid, measure, and calculate with 2 logarithmic equations of external standard, promptly.

Respectively above-mentioned three batches of Radix Astragali total saponinss are carried out assay, the results are shown in Table 2-1.

The assay result and the yield of table 2-1 Radix Astragali total saponins

The preparation of embodiment 2 astragalus polysaccharidess and discriminating and assay

The preparation of astragalus polysaccharides

Get Milkvetch Root, add 7 times of amount 70% ethanol extraction secondaries, each 2 hours, extracting solution discards, the slag extracting in water secondary of getting it filled, merge extractive liquid,, the ratio that is concentrated into extracting liquid volume and raw medicinal herbs is 1.05:1, add ethanol precipitation and make and contain the alcohol amount and reach 70%, filter, must precipitate, precipitation 70% washing with alcohol, the dissolving of reuse suitable quantity of water filters, and filtrate is crossed macroporous resin, the water eluting, collect water lotion, water lotion is concentrated into medicine liquid volume, add ethanol and make and contain alcohol and measure and reach 70% with the medical material ratio is 1:2.5, must precipitate, to precipitate with 95% ethanol and washing with acetone dehydration, drying under reduced pressure (60 ℃), promptly.

Prepare three batches of astragalus polysaccharidess respectively, yield sees Table 2-2.

The discriminating of astragalus polysaccharides

(1) gets the about 0.2mg of this product, after adding water 5ml dissolving, add 5 of alkaline cupric tartrate test solutions, heating promptly produces red precipitate, cooling, filter, get filtrate add 1 of hydrochloric acid make acid, heating in water bath 10 minutes, put cold, regulate pH value to neutral, add alkaline cupric tartrate test solution 0.5ml, heating in water bath promptly produces red copper oxidule precipitation.

(2) get the about 0.2g of this product, add water 2ml dissolving after, add 5% alpha-Naphthol alcoholic solution 0.5ml and shake up, slowly add sulphuric acid 3ml, two liquid level intersection displaing amaranth rings.

Respectively above-mentioned three batches of astragalus polysaccharidess are carried out identification experiment, the result all meets the requirements.

The assay of astragalus polysaccharides

The preparation of standard solution takes by weighing the glucose 100mg that is dried to constant weight through 105 ℃, and accurate the title decides, and puts in the 100ml measuring bottle, is dissolved in water, and is diluted to scale, shakes up.Precision is measured 10ml, puts in the 100ml measuring bottle, adds water to scale, shakes up, and is standby.

The drafting precision of standard curve is measured standard solution 0.1,0.2,0.3,0.4,0.5,0.6ml totally 6 parts, put respectively in the 25ml measuring bottle, add water to 2.0ml, and add phenol solution and (get phenol 300g, aluminium flake 0.3g, sodium bicarbonate 0.15g, mix distillation, collect 182 ℃ of fractions, be mixed with 5% aqueous solution) 1.0ml, shake up, drip concentrated sulphuric acid 5.0ml rapidly, shake up, placed 5 minutes, put in the water-bath and heated 15 minutes, take out, be cooled to room temperature rapidly, in addition with the same operation repetitive of 2.0ml water as blank, measure absorption value at 490nm wavelength place, calculate regression equation.

Algoscopy is got this product 0.5g and is put in the 25ml measuring bottle, and the method under the sighting target directrix curve drafting item is measured absorption value, according to the content of regression equation calculation polysaccharide from " adding water to 2.0ml " in accordance with the law.

Respectively above-mentioned three batches of astragalus polysaccharidess are carried out assay, the results are shown in Table 2-2.

The assay result and the yield of table 2-2 astragalus polysaccharides

The preparation of embodiment 3 Radix Rhodiolae extracts and discriminating and assay

The preparation of Radix Rhodiolae extract

Get Radix Rhodiolae medical material 20kg, be ground into coarse powder, add 70% alcohol reflux three times, each 1.5 hours, merge extractive liquid, filtered, filtrate recycling ethanol extremely every 2ml contains the 1g raw medicinal herbs, with 2 times of amount defat with petroleum ether, discards petroleum ether liquid, the water saturated n-butanol extraction of reuse is evaporated to the thick paste shape, is added on the macroporous resin of handling well in advance, water and Different concentrations of alcohol eluting successively, decompression recycling ethanol to relative density is 1.03～1.06 (60 ℃), spray drying, promptly.

Prepare three batches of Radix Rhodiolae extracts respectively, yield sees Table 2-3.

The discriminating of Radix Rhodiolae extract

Get this product 0.1g, add methanol 10ml, supersound process 30min shakes up, and filters, and filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Radix Rhodiolae medical material 1g, shines medical material solution in pairs with legal system.Drawing above-mentioned two kinds of each 5ul of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with lower floor's solution of chloroform-methanol-acetone-water (6:3:1:1), launches, and takes out, and dries, and puts in the iodine vapor smoked.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Above-mentioned three batches of Radix Rhodiolae extracts are carried out identification experiment, and the result all meets the requirements.

The assay of Radix Rhodiolae extract

The assay of total phenols

It is an amount of that the preparation precision of reference substance solution takes by weighing the gallic acid reference substance, puts in the brown measuring bottle, adds water and make the solution that every 1ml contains gallic acid 0.05mg, promptly.

The preparation precision of standard curve is measured reference substance solution 0.5ml, 1.0ml, 2.0ml, 3.0ml, 4.0ml, 5.0ml, put respectively in the brown measuring bottle of 25ml, molybdenum wolframic acid test solution 1ml respectively phosphorates, add water 11.5ml, 11ml, 10ml, 9ml, 8ml, 7ml more respectively, be diluted to scale with 29% sodium carbonate liquor, shake up, placed 30 minutes, with the reagent corresponding is blank, ultraviolet visible spectrophotometry is measured absorbance at 760nm wavelength place, be vertical coordinate with the absorbance, concentration is abscissa, the drawing standard curve.

The preparation precision of need testing solution takes by weighing Radix Rhodiolae extract 25mg, puts in the 25ml measuring bottle, adds 60% ethanol to scale, shakes up, and sample is dissolved fully, and the accurate 2ml that draws puts in the 25ml measuring bottle, adds water to scale, shakes up, promptly.

The algoscopy precision is measured need testing solution 2ml, put in the brown measuring bottle of 25ml, method under the preparation of sighting target directrix curve, from " adding P-Mo-Wo acid test solution 1ml ", add water 10ml, measure absorbance in accordance with the law, from standard curve, read the amount (mg) of gallic acid in the need testing solution, calculate, promptly.

The assay of rhodioside

Chromatographic condition and system suitability experiment are filler with octadecylsilane chemically bonded silica; With methanol-water (15:85) is mobile phase; The detection wavelength is 275nm.Number of theoretical plate calculates by the rhodioside peak should be not less than 1500.

The preparation precision of reference substance solution takes by weighing the rhodioside reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, promptly.

The preparation precision of need testing solution takes by weighing this product 0.1g, grinds well, and puts in the tool plug conical flask, accurate methanol 10ml, the close plug of adding, shake up, claim decide weight, supersound process 30min is put coldly, and weight decided in title again, supply with methanol and to subtract weight loss, shake up, filter, get subsequent filtrate, promptly.

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Above-mentioned three batches of Radix Rhodiolae extracts are carried out assay, the results are shown in Table 2-3.

The assay result and the yield of table 2-3 Radix Rhodiolae extract

The preparation of embodiment 4 Rhizoma Smilacis Chinensis total saponinss and discriminating and assay

The preparation of Rhizoma Smilacis Chinensis total saponins

Get Rhizoma Smilacis Chinensis medical material 30kg, thinly slice, add 70% alcohol reflux three times, each 2 hours, merge extractive liquid, filters, and filtrate recycling ethanol also is concentrated into nothing alcohol flavor, thin up becomes every 1ml to contain crude drug 2g, put coldly, the n-butyl alcohol jolting that adds 1/2 volume is extracted 3 times, merges n-butanol extracting liquid, decompression and solvent recovery, and vacuum drying, get extract powder and add the suitable quantity of water dissolving, be added on the resin column of having handled well, the flushing in 3～4BV/ hour of elder generation's water is to closely colourless, reuse 70% ethanol with 2～3BV/ hour towards post, collect eluent, reclaim ethanol and be concentrated into the thick paste of relative density 1.30～1.35, vacuum drying, promptly.

Prepare three batches of Rhizoma Smilacis Chinensis total saponinss respectively, yield sees Table 2-4.

The discriminating of Rhizoma Smilacis Chinensis total saponins

Get this product 0.1g, add ethanol 50ml, supersound process 30 minutes, filter, filtrate adds hydrochloric acid 5ml, reflux 2 hours, put coldly, transfer to neutrality, steam to there not being the alcohol flavor with 40% sodium hydroxide solution, residue adds hot water 40ml makes dissolving, extract 2 times (40ml, 30ml), merge extractive liquid,, evaporate to dryness with the dichloromethane jolting, residue adds methanol 1ml makes dissolving, as need testing solution.Other gets the diosgenin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution.Drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with cyclohexane extraction-ethyl acetate (4:1), launches, and takes out, and dries, and spray is with 10% ethanol solution of sulfuric acid, 105 ℃ be heated to speckle develop the color clear.In the test sample chromatograph, with reference substance chromatograph relevant position on, show the speckle of same color.

Above-mentioned three batches of Rhizoma Smilacis Chinensis total saponinss are carried out identification experiment, and the result all meets the requirements.

The assay of Rhizoma Smilacis Chinensis total saponins

The assay of Rhizoma Smilacis Chinensis total saponins glycosides

The preparation precision of standard solution takes by weighing Sarsasapogenin standard substance 10mg, puts in the 10ml measuring bottle, adds the chloroform dissolving and is diluted to scale, shakes up, promptly.

The above-mentioned standard solution 10 of the accurate absorption of the drafting of standard substance curve, 20,40,60,80,100 μ l place the 25ml nessler colorimetric tube, fling to solvent, add freshly prepared 5% vanillin-glacial acetic acid solution 0.4ml, perchloric acid 1.6ml, shake up, placed 5 minutes, put in the boiling water bath and developed the color 15 minutes, take out, put immediately and be cooled to room temperature in the ice bath, add the 8ml glacial acetic acid, shake up, spectrophotography, measuring absorbance respectively at 605 ± 2nm place, is vertical coordinate with the absorbance, and the sampling amount of Sarsasapogenin standard substance is an abscissa, the drawing standard curve calculates regression equation.

The algoscopy precision takes by weighing this product 20mg, put in the 10ml measuring bottle, add dissolve with methanol and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 50 μ l, puts in the 25ml nessler colorimetric tube, puts water bath method, put cold, method under the sighting target directrix curve drafting item is measured absorption value, according to the content of regression equation calculation total saponins from " adding freshly prepared 5% vanillin-glacial acetic acid solution 0.4ml " in accordance with the law.

Above-mentioned three batches of Rhizoma Smilacis Chinensis total saponinss are carried out assay, the results are shown in Table 2-4.

The assay result and the yield of table 2-4 Rhizoma Smilacis Chinensis extract

The preparation of embodiment 5 HHB injection

Prescription:

HHB1 injection formula 1:

HHB1 injection formula 2:

HHB2 injection formula 1:

HHB2 injection formula 2:

Concrete steps:

Carry and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse; Get the water for injection of dosing amount 80%, add the Tween-80 stirring and dissolving, add Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract and the Rhizoma Smilacis Chinensis total saponins of recipe quantity then, the heated and stirred dissolving fully; Benefit adds to the full amount of water for injection; The injection-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes; Through sand filtration rod filtering decarbonization, measure the also pH value of regulator solution; Microporous filter membrane fine straining through 0.45 μ m; Check the clarity of solution, the semi-finished product chemical examination; With filled with solution, sealing by fusing in glass ampule; 100 ℃ of flowing steam sterilizations 30 minutes; While hot sample being put into 0.01% methylene blue solution hunts leak; Lamp inspection, finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 6 injection HHB

Prescription:

Injection HHB1 prescription 1:

Injection HHBI prescription 2:

Injection HHB2 prescription 1:

Injection HHB2 prescription 2:

Concrete steps:

At first vessel that dosing is used and antibiotic glass bottle, plugs etc. carry out aseptic process; Take by weighing raw material and adjuvant according to recipe quantity; Get the sterile water for injection of dosing amount 80%, add the Tween-80 stirring and dissolving, then Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract and Rhizoma Smilacis Chinensis total saponins are added the heated and stirred dissolving fully, add the dissolving of mannitol heated and stirred more fully, add sterile water for injection to full dose; The injection-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes; Through sand filtration rod filtering decarbonization, measure the also pH value of regulator solution; ) through the microporous filter membrane fine straining of 0.22 μ m; Check the clarity of solution, the semi-finished product chemical examination; Be sub-packed in the antibiotic glass bottle half tamponade; Sample is put into the freeze dryer lyophilization;-40 ℃ of pre-freezes 4 hours, low-temperature vacuum drying-40 ℃～0 ℃ 18 hours was warming up to 20 ℃ of vacuum dryings 4 hours then; Lyophilizing finishes, and lid is rolled in tamponade; Finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 7 HHB sodium chloride injections

Prescription:

HHB1 sodium chloride injection prescription 1:

HHB1 sodium chloride injection prescription 2:

HHB2 sodium chloride injection prescription 1:

HHB2 sodium chloride injection prescription 2:

Concrete steps:

Handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse; Get the water for injection of dosing amount 20%, add the Tween-80 stirring and dissolving, then Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract and Rhizoma Smilacis Chinensis total saponins are added the heated and stirred dissolving fully, sodium chloride is complete with the water for injection dissolving of dosing amount 40%; Merge above-mentioned solution, benefit adds to the full amount of water for injection; The injection-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes; Through sand filtration rod filtering decarbonization, measure the also pH value of regulator solution; Microporous filter membrane fine straining through 0.45 μ m; Check the clarity of solution, the semi-finished product chemical examination; Fill is in the infusion bottle of 100ml; 115 ℃ of pressure sterilizings 30 minutes; Lamp inspection, finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 8 HHB glucose injections

Prescription:

HHB1 glucose injection prescription 1:

HHB1 glucose injection prescription 2:

HHB2 glucose injection prescription 1:

HHB2 glucose injection prescription 2:

Concrete steps:

Carry and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse; Get the water for injection of dosing amount 20%, add the Tween-80 stirring and dissolving, then Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract and Rhizoma Smilacis Chinensis total saponins are added the heated and stirred dissolving fully, glucose is complete with the water for injection dissolving of dosing amount 40%: merge above-mentioned solution, benefit adds to the full amount of water for injection; The injection-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes; Through sand filtration rod filtering decarbonization, measure the also pH value of regulator solution; Microporous filter membrane fine straining through 0.45 μ m; Check the clarity of solution, the semi-finished product chemical examination; Fill is in the infusion bottle of 100ml; 115 ℃ of pressure sterilizings 30 minutes; Lamp inspection, finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 9 HHB sheets

Prescription:

HHB1 tablet recipe 1:

HHB1 tablet recipe 2:

HHB2 tablet recipe 1:

HHB2 tablet recipe 2:

Concrete steps:

It is standby that Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract and Rhizoma Smilacis Chinensis total saponins were pulverized 100 mesh sieves; Take by weighing raw material and adjuvant according to recipe quantity; Hypromellose 2% the aqueous solution made soluble in water is standby; With Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract, Rhizoma Smilacis Chinensis total saponins, starch, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material; Cross 20 mesh sieve system granules; Granule is dried under 60 ℃ condition; Dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously; Sampling, the semi-finished product chemical examination; According to the definite sheet weight sheet of chemical examination; Finished product is examined entirely, the packing warehouse-in.

The capsular preparation of embodiment 10 HHB

Prescription:

HHB1 capsule prescription 1:

HHB1 capsule prescription 2:

HHB2 capsule prescription 1:

HHB2 capsule prescription 2:

Concrete steps:

It is standby that Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract and Rhizoma Smilacis Chinensis total saponins were pulverized 100 mesh sieves; Take by weighing raw material and adjuvant according to recipe quantity; Hypromellose 2% the aqueous solution made soluble in water is standby; With Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract, Rhizoma Smilacis Chinensis total saponins, starch, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material; Cross 20 mesh sieve system granules; Granule is dried under 60 ℃ condition; Dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously; Sampling, the semi-finished product chemical examination; The loading amount of determining according to chemical examination incapsulates; Finished product is examined entirely, the packing warehouse-in.

The particulate preparation of embodiment 11 HHB

Prescription:

HHB1 granule prescription 1:

HHB1 granule prescription 2;

HHB2 granule prescription 1:

HHB2 granule prescription 2:

Concrete steps:

It is standby that sucrose was pulverized 100 mesh sieves, and it is standby that Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract and Rhizoma Smilacis Chinensis total saponins were pulverized 100 mesh sieves; Take by weighing raw material and adjuvant according to recipe quantity; With the method mix homogeneously that Radix Astragali total saponins (perhaps astragalus polysaccharides), Radix Rhodiolae extract, Rhizoma Smilacis Chinensis total saponins and Icing Sugar, correctives progressively increase with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material; Cross 20 mesh sieve system granules; Granule is dried under 60 ℃ condition; Dried granule is crossed 18 mesh sieve granulate; Sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule; Packing; Finished product is examined entirely, the packing warehouse-in.

Claims

1, a kind of pharmaceutical composition that improves disordered brain function is characterized in that, said composition is mainly made by following bulk drugs: 400～10000 parts of the Radixs Astragali, 100～2000 parts of Radix Rhodiolaes, 150～3000 parts of Rhizoma Smilacis Chinensiss.

2, pharmaceutical composition as claimed in claim 1 is characterized in that, the weight portion of each crude drug is: 1000～5000 parts of the Radixs Astragali, 200～1000 parts of Radix Rhodiolaes, 300～1500 parts of Rhizoma Smilacis Chinensiss.

3, pharmaceutical composition as claimed in claim 2 is characterized in that, the weight portion of each crude drug is: 2000 parts of the Radixs Astragali, 400 parts of Radix Rhodiolaes, 600 parts of Rhizoma Smilacis Chinensiss.

4, as the described preparation of drug combination method of the arbitrary claim of claim 1～3, it is characterized in that, the described Radix Astragali, Radix Rhodiolae, Rhizoma Smilacis Chinensis with The suitable solvent and method separately or mixed extraction processing obtain extract, total extract is processed into clinically arbitrary or pharmaceutically acceptable dosage form with mixing acceptable accessories again; Contained main effective ingredient is Radix Astragali total saponins, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins in the described total extract, perhaps is astragalus polysaccharides, Radix Rhodiolae total phenols material, Rhizoma Smilacis Chinensis total saponins, and the total content of contained main effective ingredient is not less than

5, pharmaceutical composition as claimed in claim 1, it is characterized in that, said composition also can be made by following bulk drugs: Radix Astragali total saponins or astragalus polysaccharides, Radix Rhodiolae extract and Rhizoma Smilacis Chinensis total saponins, its weight portion is: 2～200 parts of Radix Astragali total saponinss, 6～160 parts of Radix Rhodiolae extracts, 2～90 parts of Rhizoma Smilacis Chinensis total saponinss perhaps are: 2～200 parts of astragalus polysaccharidess, 6～160 parts of Radix Rhodiolae extracts, 2～90 parts of Rhizoma Smilacis Chinensis total saponinss.

6, pharmaceutical composition as claimed in claim 5, it is characterized in that, the weight portion of each crude drug is: 5～100 parts of Radix Astragali total saponinss, 12～80 parts of Radix Rhodiolae extracts, 3～45 parts of Rhizoma Smilacis Chinensis total saponinss perhaps are: 5～100 parts of astragalus polysaccharidess, 12～80 parts of Radix Rhodiolae extracts, 3～45 parts of Rhizoma Smilacis Chinensis total saponinss.

7, pharmaceutical composition as claimed in claim 6, it is characterized in that, the weight portion of each crude drug is: 10～40 parts of Radix Astragali total saponinss, 24～32 parts of Radix Rhodiolae extracts, 6～18 parts of Rhizoma Smilacis Chinensis total saponinss perhaps are: 10～40 parts of astragalus polysaccharidess, 24～32 parts of Radix Rhodiolae extracts, 6～18 parts of Rhizoma Smilacis Chinensis total saponinss.

8, as claim 5,6 or 7 described arbitrary pharmaceutical compositions, it is characterized in that the content of total saponins is not less than 30% in the described Radix Astragali total saponins, wherein the content of astragaloside is not less than 1.0%; The content of polysaccharide is not less than 35% in the astragalus polysaccharides; The total phenol property material is not less than 50% in the Radix Rhodiolae extract, and wherein the content of rhodioside is not less than 3.0%; The content of total saponins is not less than 20% in the Rhizoma Smilacis Chinensis total saponins.

9,, be used for improving the application of the medicine of brain function in preparation as claim 1～3, the described pharmaceutical composition of 5～7 arbitrary claim.

10, as claim 1～3, the described pharmaceutical composition of 5～7 arbitrary claim, it is characterized in that said composition and mixing acceptable accessories are made clinically arbitrary or pharmaceutically acceptable dosage form.