[summary of the invention]
The object of the present invention is to provide a kind of pharmaceutical composition with antidepressant, angst resistance effect.
Another purpose of the present invention provides a kind of preparation of drug combination method with antidepressant, angst resistance effect.
The crude drug of pharmaceutical composition of the present invention is: Radix Bupleuri 6-15 part and Fructus Gardeniae 5-15 part; And in Radix Angelicae Sinensis 3-15 part or Rhizoma Chuanxiong 3-15 part one.
Be preferably: 10 parts of Radix Bupleuri, 10 parts of Fructus Gardeniaes, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs.
The crude drug of pharmaceutical composition of the present invention can also be: Radix Bupleuri 6-15 part and Cortex Moutan 5-20 part; And in Radix Angelicae Sinensis 3-15 part or Rhizoma Chuanxiong 3-15 part one.
Be preferably: 10 parts of Radix Bupleuri, 10 parts of Cortex Moutans, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs.
The crude drug of pharmaceutical composition of the present invention can also be: as 10 parts of 10 parts of the Radix Bupleuri of monarch drug and Fructus Gardeniaes, and 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, and as Pericarpium Citri Reticulatae 3-10 part or Rhizoma Cyperi 3-15 part of ministerial drug.
Be preferably: 10 parts of Radix Bupleuri, 10 parts of Fructus Gardeniaes, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, 10 parts of 6 parts of Pericarpium Citri Reticulataes or Rhizoma Cyperis.
The crude drug of pharmaceutical composition of the present invention can also be: as 10 parts of 10 parts of the Radix Bupleuri of monarch drug and Fructus Gardeniaes, and 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, as Pericarpium Citri Reticulatae 3-10 part or Rhizoma Cyperi 3-15 part of ministerial drug, and as Fructus Schisandrae Chinensis 5-20 part of adjuvant drug.
Be preferably: 10 parts of Radix Bupleuri, 10 parts of Fructus Gardeniaes, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, 10 parts of 6 parts of Pericarpium Citri Reticulataes or Rhizoma Cyperis, 10 parts of Fructus Schisandrae Chinensis.
The crude drug of pharmaceutical composition of the present invention can also be: as 10 parts of 10 parts of the Radix Bupleuri of monarch drug and Fructus Gardeniaes, and 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, as Pericarpium Citri Reticulatae 3-10 part or Rhizoma Cyperi 3-15 part and Rhizoma Coptidis 3-10 part of ministerial drug, and as Fructus Schisandrae Chinensis 5-20 part of adjuvant drug.
Be preferably: 10 parts of Radix Bupleuri, 10 parts of Fructus Gardeniaes, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, 10 parts of 6 parts of Pericarpium Citri Reticulataes or Rhizoma Cyperis, 5 parts of Rhizoma Coptidis, 10 parts of Fructus Schisandrae Chinensis.
The crude drug of pharmaceutical composition of the present invention can also be: as 10 parts of 10 parts of the Radix Bupleuri of monarch drug and Fructus Gardeniaes, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, as Pericarpium Citri Reticulatae 3-10 part or Rhizoma Cyperi 3-15 part and Rhizoma Coptidis 3-10 part of ministerial drug, and as Fructus Schisandrae Chinensis 5-20 part and Radix Codonopsis 3-15 part of adjuvant drug.
Be preferably: 10 parts of Radix Bupleuri, 10 parts of Fructus Gardeniaes, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, 10 parts of 6 parts of Pericarpium Citri Reticulataes or Rhizoma Cyperis, 5 parts of Rhizoma Coptidis, 10 parts of Fructus Schisandrae Chinensis, 10 parts of Radix Codonopsis.
The crude drug of pharmaceutical composition of the present invention can also be: as 10 parts of 10 parts of the Radix Bupleuri of monarch drug and Fructus Gardeniaes, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, as Pericarpium Citri Reticulatae 3-10 part or Rhizoma Cyperi 3-15 part of ministerial drug, Rhizoma Coptidis 3-10 part and Rhizoma Pinelliae 6-20 part, and as Fructus Schisandrae Chinensis 5-20 part and Radix Codonopsis 3-15 part of adjuvant drug.
Be preferably: 10 parts of Radix Bupleuri, 10 parts of Fructus Gardeniaes, 10 parts of 10 parts of Radix Angelicae Sinensis or Rhizoma Chuanxiongs, 10 parts of 6 parts of Pericarpium Citri Reticulataes or Rhizoma Cyperis, 5 parts of Rhizoma Coptidis, 10 parts of the Rhizoma Pinelliaes, 10 parts of Fructus Schisandrae Chinensis, 10 parts of Radix Codonopsis.
The raw medicinal material that the present invention uses is:
Radix Bupleuri of the present invention is the dry root of umbelliferae bupleurum Bupleurum chinense DC. or Radix Bupeuri Scorzonerfolii. Bupleurumscorzonerfolium Willd..
Of the present invention when the dry root that is classified as umbelliferae angelica Angelica sinensis (Oliv.) Diels.
Rhizoma Chuanxiong of the present invention is the dry rhizome of samphire Rhizoma Chuanxiong Ligusticum chuanxiong Hort..
Fructus Gardeniae of the present invention is dry mature fruit and the processed product thereof of Maguireothamnus speciosus Fructus Gardeniae Gardenia jasminoides Ellis.
Cortex Moutan of the present invention is the dry root bark of ranunculaceae peony Paeonia suffruticosa Andr..
Pericarpium Citri Reticulatae of the present invention is the dry mature skin of rutaceae orange Citrus reticulate Blanco and variety thereof.
Rhizoma Cyperi of the present invention is dry rhizome and the processed product thereof of sedge dried tuber Cyperus rotundus L..
Rhizoma Coptidis of the present invention is the dry rhizome of ranunculaceae plant Rhizoma Coptidis Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao Coptis deltoideaC.Y.Cheng et Hsiao or Coptis Teeta Wall Coptis teeta Wall., comprises flavor company, refined company, Coptis Teeta Wall.
Fructus Schisandrae Chinensis of the present invention is the dry mature fruit of magnoliaceae schisandra Schisandra chinensis (Turcz.) Baill..
Radix Codonopsis of the present invention is the dry root of campanulaceae plant Radix Codonopsis Codonopsis pilosula (Franch.) Nannf., plain flower Radix Codonopsis Codonopsis pilosula Nannf.var.modesta (Nannf.) L.T.Shen or radix codonpsis tangshen Codonopsis tangshen Oliv..
The Rhizoma Pinelliae of the present invention is dry tuber and the processed product thereof of aroid Rhizoma Pinelliae Pinellia ternate (Thunb.) Breit..
Semen Ziziphi Spinosae of the present invention is the dry mature seed of Rhamnaceae plant Ziziphi Spinosae Ziziphus jujube Mill.Var.spinosa (Bunge) Hu exH.F.Chou.
The Radix Paeoniae Alba of the present invention is the dry root of ranunculaceae plant Radix Paeoniae Paeonia lactiflora Pall..
Semen Platycladi of the present invention is the dry mature kernal of Cupressaceae plant Cacumen Platycladi Platycladus orientalis (L.) Franco.
Pharmaceutical composition of the present invention can adopt the conventional method of Chinese medicine preparation to be prepared into any conventional oral preparations.For example these raw medicinal material pulverize mix homogeneously can be made powder takes after mixing it with water; Can be with these raw medicinal materials decocting together or ethanol extraction; Also these raw medicinal materials can be utilized modern technologies to extract, as passing through supercritical carbon dioxide (SFE-CO
2) extraction or ultrasonic extraction etc., concentrate drying then.But for each crude drug that makes this pharmaceutical composition is brought into play drug effect better, preferably the Radix Angelicae Sinensis in all medical materials, Rhizoma Chuanxiong, the Rhizoma Pinelliae, Rhizoma Coptidis, Fructus Schisandrae Chinensis, Rhizoma Cyperi are carried out ethanol extraction, the Fructus Gardeniae in all medical materials, Radix Codonopsis, Pericarpium Citri Reticulatae, Radix Bupleuri are carried out decocting.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Fructus Gardeniae; And Radix Angelicae Sinensis totally 3 flavors are during medical materials, the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) Radix Angelicae Sinensis of described weight proportion is added the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) Radix Bupleuri, the Fructus Gardeniae with described weight proportion adds 8~15 times of water gagings decoctions 1~3 time together, and each 1~3 hour, filtration, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, and filters, and filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Fructus Gardeniae; And Rhizoma Chuanxiong totally 3 flavors are during medical materials, the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) Rhizoma Chuanxiong of described weight proportion is added the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) Radix Bupleuri, the Fructus Gardeniae with described weight proportion adds 8~15 times of water gagings decoctions 1~3 time together, and each 1~3 hour, filtration, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, and filters, and filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Cortex Moutan; And Radix Angelicae Sinensis totally 3 flavors are during medical materials, the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) Radix Angelicae Sinensis, the Cortex Moutan of described weight proportion added the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) Radix Bupleuri with described weight proportion adds 8~15 times of water gagings decoctions 1~3 time, and each 1~3 hour, filtration, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, and filters, and filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Cortex Moutan; And Rhizoma Chuanxiong totally 3 flavors are during medical materials, the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) Rhizoma Chuanxiong, the Cortex Moutan of described weight proportion added the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) Radix Bupleuri with described weight proportion adds 8~15 times of water gagings decoctions 1~3 time, and each 1~3 hour, filtration, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, and filters, and filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Fructus Gardeniae; Radix Angelicae Sinensis or Rhizoma Chuanxiong; And Pericarpium Citri Reticulatae or Rhizoma Cyperi be during totally 4 flavor medical materials, and the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) Rhizoma Chuanxiong of described weight proportion or Radix Angelicae Sinensis are added the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) with the Pericarpium Citri Reticulatae or the Rhizoma Cyperi of described weight proportion, and Radix Bupleuri and Fructus Gardeniae add 8~15 times of water gagings together and decoct 1~3 time, each 1~3 hour, filters, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, filter, filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Fructus Gardeniae; Radix Angelicae Sinensis or Rhizoma Chuanxiong; Pericarpium Citri Reticulatae or Rhizoma Cyperi; And Fructus Schisandrae Chinensis totally 5 flavors are during medical materials, the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) Rhizoma Chuanxiong of described weight proportion or Radix Angelicae Sinensis, Fructus Schisandrae Chinensis are added the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) with the Pericarpium Citri Reticulatae or the Rhizoma Cyperi of described weight proportion, and Radix Bupleuri and Fructus Gardeniae add 8~15 times of water gagings together and decoct 1~3 time, each 1~3 hour, filters, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, filter, filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Fructus Gardeniae; Radix Angelicae Sinensis or Rhizoma Chuanxiong; Pericarpium Citri Reticulatae or Rhizoma Cyperi; Fructus Schisandrae Chinensis; And Rhizoma Coptidis totally 6 flavors are during medical materials, the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) Rhizoma Chuanxiong of described weight proportion or Radix Angelicae Sinensis and Fructus Schisandrae Chinensis and Rhizoma Coptidis are added the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) Pericarpium Citri Reticulatae of described weight proportion or Rhizoma Cyperi and Radix Bupleuri and Fructus Gardeniae are added 8~15 times of water gagings together and decoct 1~3 time, each 1~3 hour, filter, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, filter, filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Fructus Gardeniae; Radix Angelicae Sinensis or Rhizoma Chuanxiong; Pericarpium Citri Reticulatae or Rhizoma Cyperi; Fructus Schisandrae Chinensis; Rhizoma Coptidis; And Radix Codonopsis totally 7 flavors are during medical materials, the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) Rhizoma Chuanxiong of described weight proportion or Radix Angelicae Sinensis and Fructus Schisandrae Chinensis and Rhizoma Coptidis are added the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) with the Pericarpium Citri Reticulatae or the Rhizoma Cyperi of described weight proportion, and Radix Bupleuri, Fructus Gardeniae and Radix Codonopsis add 8~15 times of water gagings together and decoct 1~3 time, each 1~3 hour, filters, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, filter, filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Preferably, if the crude drug of pharmaceutical composition of the present invention is a Radix Bupleuri; Fructus Gardeniae; Radix Angelicae Sinensis or Rhizoma Chuanxiong; Pericarpium Citri Reticulatae or Rhizoma Cyperi; Fructus Schisandrae Chinensis; Rhizoma Coptidis; Radix Codonopsis; And the Rhizoma Pinelliae totally 8 flavors are during medical materials, the preparation method of its active component is as follows:
1) take by weighing each crude drug, standby.
2) with the Rhizoma Chuanxiong or the Radix Angelicae Sinensis of described weight proportion, and Fructus Schisandrae Chinensis, Rhizoma Coptidis and the Rhizoma Pinelliae add the ethanol extraction 1~4 time of 6~12 times of amounts 40%~80%, each 0.5~2 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, dry extract;
3) with the Pericarpium Citri Reticulatae or the Rhizoma Cyperi of described weight proportion, and Radix Bupleuri, Fructus Gardeniae and Radix Codonopsis add 8~15 times of water gagings together and decoct 1~3 time, each 1~3 hour, filters, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, filter, filtrate is concentrated, dry, gets component 2.
4) merge component 1 and component 2, be ground into powder, mix homogeneously just has been prepared into the active component of medicine of the present invention.
Needed various conventional adjuvants when the active component of pharmaceutical composition of the present invention can add the preparation different dosage form, method of Chinese medicinal as routines such as disintegrating agent, lubricant, binding agents is prepared into any dosage form for oral administration commonly used, as granule, electuary, tablet, drop pill, pill, capsule, soft capsule, oral liquid, mixture etc.
Pharmaceutical composition of the present invention has functions such as antidepressant, anxiety, can be used for treating depression, anxiety neurosis, comprises the described melancholia of Chinese medicine, is insomnia, disease such as headache, cardiopalmus.
[novelty of invention]
Although Chinese medicine depression and anxiety neurosis have accumulated many clinical experiences, the new drug that is of no curative effect definite so far comes out.The inventor thinks qi depression to blood stasis (or double stagnation of phlegm), strongly fragrant and heat-transformation is the crucial pathogenesis of above-mentioned disease, and faces in the traditional Chinese medical science that the unexpected drug regimen is made up of Radix Bupleuri, Rhizoma Chuanxiong or Radix Angelicae Sinensis, Fructus Gardeniae or Cortex Moutan found has the good clinical effect aspect depression and the anxiety neurosis treating in the card; Its dominant ideas are that Radix Bupleuri is soothing the liver, circulation of qi promoting, resolving depression, Rhizoma Chuanxiong or Radix Angelicae Sinensis blood circulation promoting and blood stasis dispelling, and Fructus Gardeniae or Cortex Moutan are let out hot and suffocating clearly, and the three is combined into monarch drug.The inventor is also by a series of experiments, produced synergism between the medicine that proof above-mentioned raw materials medicine makes, make it have unique curative effect to depression and anxiety neurosis, Radix Angelicae Sinensis and Rhizoma Chuanxiong, Fructus Gardeniae and Cortex Moutan play same function in this basis side, therefore be used interchangeably.This combination does not all have open in the prior art, belongs to a kind of medicine of brand-new combination.
The inventor on this basis, determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs thinking in conjunction with Chinese medicine, at different patients' individual difference (as the different causes of disease, the concurrent or syndrome that occurs together, perhaps the life-time service said medicine makes up the human righteousness that may dissipate, cause curative effect of medication reduction etc.), on the medicine basis of above-mentioned monarch drug, add other crude drug as ministerial drug, adjuvant drug or messenger drug, can obtain higher effective percentage or keep more persistent clinical efficacy.As: 1, to irritability stasis person can add Pericarpium Citri Reticulatae, Rhizoma Cyperi is a ministerial drug, with help Radix Bupleuri, Rhizoma Chuanxiong or Radix Angelicae Sinensis circulation of qi promoting, invigorate blood circulation, the merit of resolving depression; 2, can add Rhizoma Coptidis to hot and suffocating more very person is minister, expels the heat-evil to help Fructus Gardeniae or Cortex Moutan; 3, cause to stagnating that water liquid fortuneization is obstructed, the patient of phlegm resistance can add Rhizoma Pinelliae drying dampness to eliminate phlegm because of gas, blood stagnation; 4, to because of using above-mentioned monarch drug or ministerial drug to cause healthy energy dissipation person, both can help, also can help with product QI invigorating, yin nourishing or invigorating YANG such as Radix Codonopsis, Radix Ginseng, Radix Panacis Quinquefolii, Radix Pseudostellariae, the Radixs Astragali with sour, puckery Fructus Schisandrae Chinensis yin and blood nourishing.Above-mentioned 2-4 class situation also usually simultaneously and see, so in order to obtain higher effective percentage or more persistent clinical efficacy, the said medicine combination also can simultaneously and be used.
Those skilled in the art all can recognize between Radix Ginseng, Radix Pseudostellariae, Radix Panacis Quinquefolii, the Radix Astragali and the Radix Codonopsis common point in the QI invigorating function aspects; Semen Ziziphi Spinosae, Semen Platycladi, the Radix Paeoniae Alba and the Fructus Schisandrae Chinensis common point aspect yin and blood nourishing; Rhizoma Coptidis, Cortex Moutan and SHANZHIZI are in the common point of letting out clearly aspect hot and suffocating, and they all can bring into play identical effect in drug regimen of the present invention, and approve between these compositionss to have unicity.
The raw medicinal material effective ingredient that Different Extraction Method extracted, the kind of toxic component and content may be different, so if same drug regimen is selected different extraction processes, the dosage ratio of its raw medicinal material also should give corresponding adjustment.For example, the raw medicinal material Rhizoma Chuanxiong water in the drug regimen of the present invention is carried and can be used the 10-15 weight portion, and alcohol extraction, supercritical extraction or supersound extraction can only need the 1-5 weight portion, but can maintain metastable level with the consumption of other raw medicinal materials of its compatibility.
Because of above-mentioned reason, other raw medicinal materials of this invention are not or/and the selection of its dosage influences realization of the present invention.
[specific embodiment]
Pharmacological evaluation:
Below further set forth the beneficial effect of pharmaceutical composition of the present invention by testing example.
1 material
1.1 animal
SPF level kunming mouse, male and female dual-purpose, body weight 20g ± 2g.
1.2 medicine and reagent
Pharmaceutical composition N1-N24 of the present invention (the crude drug kind of each pharmaceutical composition is seen note, and the consumption of each crude drug is referring to the preferable amount of each crude drug that provides in the summary of the invention), dosage 0.28g crude drug/Kg body weight (being equivalent to clinical equivalent dosage); SHULE ANDING PIAN, Hubei Pharmaceutical Co., Ltd.'s product (commercial); Pentobarbital sodium, China Medicine (Group) Shanghai Chemical Reagent Co., (commercial); The Chlorimipramine sheet, 25mg/ sheet (commercial).Administering mode: gastric infusion, the blank group gives isometric distilled water.
1.3 instrument
Mouse tail suspension balance bracket, tank, digital vedio recording instrument, mice light and shade case apparatus, overhead cross labyrinth device, Chronograph
2 methods and result
2.1 statistical method
Adopt the SPSS10.0 statistical software to carry out statistical procedures.Statistical method measurement data One-way-ANOVA compares between many groups in twos, with LSD (Least-Signficant-Difference) statistics, and enumeration data Pearson Chi-square statistics.
2.2 the influence of outstanding tail mice behavior
Get 372 of body weight 18-22g male mices, be divided into 31 groups (12 every group) at random, blank group (giving isometric distilled water), positive controls (Chlorimipramine 0.04g/kg), the Radix Bupleuri group, the Rhizoma Chuanxiong group is worked as grouping, Fructus Gardeniae group, Cortex Moutan group, N1-N24 group.Gastric infusion, every day 1 time, each administration 0.4mL/, continuous 30 days.The single cage of experiment animal the previous day is raised, and water is can't help in fasting.Behind the last administration 45min, mouse tail is sticked at outstanding rod at distance tail point 2cm place, its head is hung downwards with adhesive plaster, hang mice apart from desktop 15cm, the outstanding tail dead time surveyed in record after adapting to 2min, manual time-keeping, interior dead time (seeing Table 1) of accumulative total 5min occur use when motionless.
The experiment of table 1 mouse tail suspension (x ± s)
Annotate: with the contrast of blank group, * P<0.05, * * P<0.01
▲: compare P<0.05 with N1-N4
2.3 influence to the behavior of forced swimming mice
Get 372 of body weight 18-22g male mices, be divided into 31 groups (12 every group) at random, blank group (giving isometric distilled water), positive controls (Chlorimipramine 0.04g/kg), the Radix Bupleuri group, the Rhizoma Chuanxiong group is worked as grouping, Fructus Gardeniae group, Cortex Moutan group, N1-N24 group.Gastric infusion, every day 1 time, each administration 0.4mL/, continuous 30 days.The single cage of experiment animal the previous day is raised, and water is can't help in fasting.Begin experiment behind the last administration 45min, during experiment mice being put into the depth of water is 20cm, and in long 22cm * wide 16cm water tank, 25 ℃ of water temperatures begin to calculate the dead time (seeing Table 2) in the 5min behind the adaptation 2min.
Table 2 mouse swimming test (x ± s)
Annotate: with the contrast of blank group, * P<0.05, * * P<0.01
▲: compare P<0.05 with N1-N4
2.4 the mice light and shade is worn the case experiment
Get 310 of body weight 18-22g male mices, be divided into 31 groups (10 every group) at random, blank group (giving isometric distilled water), positive controls (estazolam, 5mg/Kg), the Radix Bupleuri group, the Rhizoma Chuanxiong group is worked as grouping, Fructus Gardeniae group, Cortex Moutan group, N1-N24 group.Gastric infusion, every day 1 time, each administration 0.4mL/, continuous 7 days.1h places camera-lucida central authorities with mice after the last administration, and the back of the body is towards the darkroom, and mice is worn the case number of times in the observed and recorded 10min.With this index (seeing Table 3) as evaluation medicine angst resistance effect.
Table 3 pair mice light and shade is worn the influence (x ± s) of case number of times
Group N dosage (g/kg) is worn the case number of times
Blank group 10 16.2 ± 2.3
Radix Bupleuri group 10 0.28 17.0 ± 2.7
Rhizoma Chuanxiong group 10 0.28 17.3 ± 2.1
When grouping 10 0.28 16.5 ± 4.0
Fructus Gardeniae organizes 10 0.28 17.4 ± 3.5
Cortex Moutan group 10 0.28 17.0 ± 4.3
Estazolam group 10 0.00 535.7 ± 12.3**
N1 10 0.28 21.0±3.2*
N2 10 0.28 21.2±4.8*
N3 10 0.28 23.4±5.0*
N4 10 0.28 23.9±4.6*
N5 10 0.28 27.9±4.6**▲
N6 10 0.28 28.6±5.2**▲
N7 10 0.28 31.4±4.9**▲
N8 10 0.28 30.6±5.3**▲
N9 10 0.28 29.8±5.3**▲
N10 10 0.28 32.4±5.6**▲
N11 10 0.28 29.8±4.7**▲
N12 10 0.28 30.2±4.3**▲
N13 10 0.28 32.7±5.5**▲
N14 10 0.28 31.3±4.9**▲
N15 10 0.28 32.5±5.4**▲
N16 10 0.28 33.6±5.6**▲
N17 10 0.28 33.8±6.5**▲
N18 10 0.28 32.1±6.0**▲
N19 10 0.28 30.9±5.2**▲
N20 10 0.28 31.1±4.7**▲
N21 10 0.28 34.5±4.0**▲
N22 10 0.28 33.3±3.4**▲
N23 10 0.28 32.9±4.9**▲
N24 10 0.28 31.6±5.7**▲
Annotate: with the contrast of blank group, * P<0.05, * * P<0.01
▲: compare P<0.05 with N1-N4
2.5 mice elevated plus-maze test
Get 310 of body weight 18-22g male mices, be divided into 31 groups (10 every group) at random, blank group (giving isometric distilled water), positive controls (estazolam, 5mg/Kg), the Radix Bupleuri group, the Rhizoma Chuanxiong group is worked as grouping, Fructus Gardeniae group, Cortex Moutan group, N1-N24 group.Gastric infusion, every day 1 time, each administration 0.4mL/, continuous 7 days.1h places labyrinth central authorities with mice after the last administration, and head is towards closure arm, and the observer is apart from the central about 1m in labyrinth.Write down the interior mice of experiment periods 5min respectively and enter number of times, the time of staying of open arms and closure arm, reach the total time of being detained at two arms.Calculate mice and enter out the number of times of arm and ask the percentage rate that accounts for always to go into arm number of times (the number of times sum that enters out arm and close arm) respectively and always go into the arm time (opening arm and closing arm holdup time sum) when arm is detained opening, with this as evaluation medicine index antianxity (seeing Table 4).
Table 4 pair mice enters the influence (x ± s) of overhead cross labyrinth open arms time, number of times
Group n dosage (g/kg) is gone into arm time percentage rate and is gone into arm number of times percentage rate
Blank group 10 4.22 ± 1.83 12.23 ± 8.56
Radix Bupleuri group 10 0.28 4.57 ± 2.40 11.73 ± 4.00
Rhizoma Chuanxiong group 10 0.28 4.42 ± 2.15 13.58 ± 3.54
When grouping 10 0.28 4.33 ± 1.96 13.50 ± 1.95
Fructus Gardeniae organizes 10 0.28 4.60 ± 1.90 12.47 ± 2.42
Cortex Moutan group 10 0.28 4.36 ± 1.81 12.33 ± 2.21
Estazolam group 10 0.00 511.63 ± 5.72** 26.76 ± 5.62**
N1 10 0.28 6.37±2.04* 15.05±3.33*
N2 10 0.28 6.79±2.83* 14.90±2.84*
N3 10 0.28 6.26±2.13* 16.02±4.64*
N4 10 0.28 6.72±2.55* 15.36±3.35*
N5 10 0.28 8.70±2.59**▲ 17.28±3.47*
N6 10 0.28 8.65±2.42**▲ 18.31±3.56*
N7 10 0.28 9.23±3.06**▲ 17.18±4.62*
N8 10 0.28 8.83±2.68**▲ 17.27±4.56*
N9 10 0.28 8.98±3.00**▲ 19.83±5.52**▲
N10 10 0.28 9.72±2.52**▲ 20.62±4.35**▲
N11 10 0.28 9.66±3.29**▲ 21.44±4.76**▲
N12 10 0.28 9.83±2.40**▲ 21.36±5.07**▲
N13 10 0.28 9.67±3.36**▲ 22.75±4.62**▲
N14 10 0.28 9.73±3.11**▲ 21.58±3.73**▲
N15 10 0.28 9.65±2.97**▲ 22.69±4.88**▲
N16 10 0.28 9.59±4.13**▲ 21.17±5.03**▲
N17 10 0.28 9.43±2.86**▲ 22.60±4.24**▲
N18 10 0.28 9.40±3.45**▲ 24.59±4.73**▲
N19 10 0.28 9.68±3.20**▲ 23.88±5.09**▲
N20 10 0.28 10.16±4.22**▲ 23.52±3.70**▲
N21 10 0.28 9.73±4.30**▲ 25.62±4.59**▲
N22 10 0.28 10.07±3.58**▲ 24.73±4.90*▲
N23 10 0.28 10.29±4.42**▲ 23.58±4.27**▲
N24 10 0.28 9.78±3.86**▲ 22.53±5.62**▲
Annotate: with the contrast of blank group, * P<0.05, * * P<0.01
▲: compare P<0.05 with N1-N4
3 conclusions
N1-N24 respectively is subjected to the reagent gastric infusion, can obviously shorten the motionless and non-swimming time of the desperate mouse tail suspension of behavior, increases the mice light and shade and wears the case number of times, improves mice and enters overhead cross labyrinth open arms time and number of times percentage rate; And the effect of N5-N24 totally is better than N1-N4.Experimental result has proved that also the combination of three kinds of crude drug of N1-N4 has produced extra synergism than the simple combination of single medical material, and, the synergism that is obtained between the N1-N4 is basic identical, having proved to be based between the N1-N4 that identical prescription thinking obtains, is the basic side and the core of pharmaceutical composition of the present invention.In addition, on the basis of this combination, ministerial drug, adjuvant drug that has increased other etc. all can make drug effect further be brought into play.Illustrate that pharmaceutical composition N1-N24 of the present invention has definite anxiety, antidepressant effect.
Note: the crude drug combination of pharmaceutical composition N1-N24 of the present invention sees the following form:
The pharmaceutical composition numbering |
The crude drug combination |
N1 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong |
N2 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis |
N3 |
Radix Bupleuri, Cortex Moutan, Rhizoma Chuanxiong |
N4 |
Radix Bupleuri, Cortex Moutan, Radix Angelicae Sinensis |
N5 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Pericarpium Citri Reticulatae |
N6 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Pericarpium Citri Reticulatae |
N7 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Rhizoma Cyperi |
N8 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Rhizoma Cyperi |
N9 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Pericarpium Citri Reticulatae, Fructus Schisandrae Chinensis |
N10 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, Fructus Schisandrae Chinensis |
N11 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Rhizoma Cyperi, Fructus Schisandrae Chinensis |
N12 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Rhizoma Cyperi, Fructus Schisandrae Chinensis |
N13 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Pericarpium Citri Reticulatae, Fructus Schisandrae Chinensis, Rhizoma Coptidis |
N14 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, Fructus Schisandrae Chinensis, Rhizoma Coptidis |
N15 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Rhizoma Cyperi, Fructus Schisandrae Chinensis, Rhizoma Coptidis |
N16 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Rhizoma Cyperi, Fructus Schisandrae Chinensis, Rhizoma Coptidis |
N17 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Pericarpium Citri Reticulatae, Fructus Schisandrae Chinensis, Rhizoma Coptidis, Radix Codonopsis |
N18 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, Fructus Schisandrae Chinensis, Rhizoma Coptidis, Radix Codonopsis |
N19 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Rhizoma Cyperi, Fructus Schisandrae Chinensis, Rhizoma Coptidis, Radix Codonopsis |
N20 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Rhizoma Cyperi, Fructus Schisandrae Chinensis, Rhizoma Coptidis, Radix Codonopsis |
N21 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Pericarpium Citri Reticulatae, Fructus Schisandrae Chinensis, Rhizoma Coptidis, Radix Codonopsis, the Rhizoma Pinelliae |
N22 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, Fructus Schisandrae Chinensis, Rhizoma Coptidis, Radix Codonopsis, the Rhizoma Pinelliae |
N23 |
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Rhizoma Cyperi, Fructus Schisandrae Chinensis, Rhizoma Coptidis, Radix Codonopsis, the Rhizoma Pinelliae |
N24 |
Radix Bupleuri, Fructus Gardeniae, Radix Angelicae Sinensis, Rhizoma Cyperi, Fructus Schisandrae Chinensis, Rhizoma Coptidis, Radix Codonopsis, the Rhizoma Pinelliae |
Preparation method:
Below enumerated the multiple method for preparing pharmaceutical composition of the present invention, but these methods only are illustrative, but not are intended to scope of the present invention is made restriction.
The granule preparation of [embodiment 1] pharmaceutical composition of the present invention
Take by weighing Radix Bupleuri 10g, Fructus Gardeniae 10g, Radix Angelicae Sinensis 10g, Rhizoma Cyperi 10g, Rhizoma Coptidis 5g, Rhizoma Pinelliae 10g, Fructus Schisandrae Chinensis 10g, Radix Codonopsis 10g, standby.
Radix Angelicae Sinensis, Fructus Schisandrae Chinensis, Rhizoma Coptidis, the Rhizoma Pinelliae are added 8 times of amount ethanol extractions of 70% 3 times, each 1 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, component 1.
Radix Bupleuri, Fructus Gardeniae, Rhizoma Cyperi, Radix Codonopsis are added 10 times of water gagings decoctions 3 times, each 1 hour, filtration, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, and filters, and filtrate is concentrated, dry, gets component 2; Merge component 1 and component 2, be ground into powder, mix homogeneously, the system granule, promptly.
The preparation tablets of [embodiment 2] pharmaceutical composition of the present invention
Take by weighing Radix Bupleuri 10g, Fructus Gardeniae 10g, Rhizoma Chuanxiong 10g, Pericarpium Citri Reticulatae 6g, Fructus Schisandrae Chinensis 10g, Rhizoma Coptidis 5g, Radix Codonopsis 10g, Rhizoma Pinelliae 10g, standby
Rhizoma Chuanxiong, Fructus Schisandrae Chinensis, Rhizoma Coptidis, the Rhizoma Pinelliae are added 8 times of amount ethanol extractions of 70% 3 times, each 1 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, component 1.
Radix Bupleuri, Fructus Gardeniae, Pericarpium Citri Reticulatae, Radix Codonopsis are added 10 times of water gagings decoctions 3 times, each 1 hour, filtration, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, and filters, and filtrate is concentrated, dry, gets component 2;
Merge component 1 and component 2, be ground into powder, mix homogeneously, tabletting, promptly.
The preparation tablets of [embodiment 3] pharmaceutical composition of the present invention
Take by weighing Radix Bupleuri 10g, Cortex Moutan 10g, Rhizoma Chuanxiong 10g, standby.
Rhizoma Chuanxiong, Cortex Moutan are added 8 times of amount ethanol extractions of 70% 3 times, each 1 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, component 1.
Radix Bupleuri is added 10 times of water gagings decoctions 3 times, each 1 hour, filtration, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, and filters, and filtrate is concentrated, dry, gets component 2;
Merge component 1 and component 2, be ground into powder, mix homogeneously, tabletting, promptly.
The capsule preparation of [embodiment 4] pharmaceutical composition of the present invention
Take by weighing Radix Bupleuri 10g, Fructus Gardeniae 10g, Radix Angelicae Sinensis 10g, Rhizoma Cyperi 10g, Rhizoma Coptidis 5g, Rhizoma Pinelliae 10g, Fructus Schisandrae Chinensis 10g, Radix Codonopsis 10g, standby, standby.
Radix Angelicae Sinensis, Fructus Schisandrae Chinensis, Rhizoma Coptidis, the Rhizoma Pinelliae are added 8 times of amount ethanol extractions of 70% 3 times, each 1 hour, filter, merging filtrate, decompression recycling ethanol, drying under reduced pressure below 60 ℃, component 1.
Radix Bupleuri, Fructus Gardeniae, Rhizoma Cyperi, Radix Codonopsis are added 10 times of water gagings decoctions 3 times, each 1 hour, filtration, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, and filters, and filtrate is concentrated, dry, gets component 2;
Merge component 1 and component 2, be ground into fine powder, cross sieve No. six, filled hard capsules, promptly.
The preparation of the oral liquid of [embodiment 5] pharmaceutical composition of the present invention
Take by weighing Radix Bupleuri 10g, Fructus Gardeniae 10g, Rhizoma Chuanxiong 10g, Pericarpium Citri Reticulatae 6g, standby.
Radix Bupleuri, Fructus Gardeniae, Rhizoma Chuanxiong, Pericarpium Citri Reticulatae are added 10 times of water gagings decoct 3 times, each 1 hour, filter, merging filtrate is concentrated into relative density 1.05~1.15 (70~85 ℃ of heat are surveyed), leaves standstill, filter, filtrate adds ethanol makes the alcohol amount of containing 60%, leaves standstill, and filters, filtrate recycling ethanol, it is an amount of to add water, filters, promptly.