CN101450103A

CN101450103A - Medicine composition for treating hypochondria and anxiety neurosis

Info

Publication number: CN101450103A
Application number: CNA2007101963711A
Authority: CN
Inventors: 张作光
Original assignee: QI YUFEN
Current assignee: QI YUFEN
Priority date: 2007-11-30
Filing date: 2007-11-30
Publication date: 2009-06-10

Abstract

The invention discloses a pharmaceutical composition or health food for treating barythymia and anxiety neurosis made from the raw materials containing ginsenoside (Rg1+Rb1), glycyrrhetic acid and chinese date cAMP, especially a pharmaceutical composition or health food for treating barythymia and anxiety neurosis with definite functions, evident effects, low side effect and high safety for long term taking. The experiments verify that: comparing with mainstream medicines for treating barythymia and anxiety neurosis in current technology, such as Paroxetine and Diazepam, the medicine in the invention achieves more remarkable anti-melancholia and anti-dysphoria effect.

Description

The pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis

Technical field

The present invention relates to one group to comprise ginsenoside (Rg1+Rb1), glycyrrhizic acid and Fructus Jujubae cyclic adenosine monophosphate (Fructus Jujubae cyclic adenosine monophosphate, Fructus Jujubae cAMP) raw material, pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis or the health food made.It is clear and definite to relate in particular to a kind of effective component, and curative effect is obvious, and side effect is low, takes safe pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis or health food for a long time.

Background technology

Mental disorder is called mental sickness again, is meant under the effect of biological, society, psychological factor, causes the brain function imbalance, and the unusual of psychomotor aspects such as perception, thinking, emotion, behavior, will and intelligence occur.Along with the development of society, mental disorder more and more is subject to people's attention, and in 10 kinds of diseases that cause the heavy burden of society, mental sickness has accounted for 4 kinds.Psychologic medicine is progressively receiving the concern of medical science colleague and society and is being endowed new understanding.And anxiety neurosis (AnxietyDisorder) and melancholia (Depression) are the common types of mental disorder, and using antianxiety drugs and antidepressant drug is treatment anxiety neurosis and hypochondriacal main method.

Anxiety neurosis is a kind of nervous disorders based on anxiety, mainly shows as anxieties such as the anxiety, anxiety of ictal or persistence, terrified uneasiness, and with symptoms such as autonomic nervous dysfunction, muscular tone and motion uneasinesses.Since Freud separated anxiety neurosis from the neurasthenia after, the various countries scholar had launched large-scale research work to anxiety neurosis, has accumulated a large amount of data.Modern medicine study thinks that many-sides such as the generation development of anxiety neurosis and neuro anatomy, the modified receptor of neurotransmitter, neuroendocrine system all have relation.

In the prior art, anxiolytic drugs is based on Benzodiazepine (Benzodiazepine) class antianxiety drugs, and its mechanism of action is to adjust a kind of activity of nerve conduction material GABA of inhibition to alleviate anxiety symptom.But can produce such as insomnia, allergy, myalgia, weakness, feel sick, side effect such as movement disorder, blurred vision, tired, chaotic, vain hope.

The melancholia is a kind of common disease, the data that The World Health Organization (WHO) provides: the melancholia is about 11% at global sickness rate, the whole world has 3.4 hundred million depressed patients approximately at present, and this numeral is still in rising trend, investigation finds that the melancholia will rise to world's second largest common disease at 20 years from now on.

In the prior art, Remeron is based on (5-HT, NE, the DA reuptake inhibitors of classes such as SSRI, SNRI, NDRI) such as fluoxetine, celo spy, Zolofts, and its mechanism of action is to alleviate melancholy symptom by component contents such as five hydroxytryptamines in the increase human nerve medium.But, the Remeron that has come out all has side effect in various degree, for example: increase homicide rate, headache, dizziness, dizzy, insomnia, drowsiness, tinnitus, xerostomia, anorexia, appetite increases, body weight rising, increased blood pressure, gastrointestinal upset, regurgitation, nauseating, vomiting, dyspepsia, diarrhoea, constipation, leg pain, skin eruption, tremble, spasm, hyperhidrosis, edema, libido reduction, sexual dysfunction etc.

Remeron such as fluoxetine has become the serious problem of paying close attention to of society in recent years, U.S. food and FAD (Food and Drug Administration, FDA) more in required in 2004 the pharmaceutical factory with market on 32 kinds of main Remerons indicate the part of its side effect and warning again, and medical personnel are emphasized that these medicines may increase the probability that child and teenager are committed suiside; And many melancholia's sufferers that treatment condition and treatment wish are arranged, because fear or be difficult to stand many side effect of existing resist melancholy agent and interrupt or refuse treating.Under this background, how to research and develop side effect of new generation low, for a long time take safe again can anti-melancholy of significant effective and medicine antianxity, the problem that has become global the world of medicine and paid close attention to.

Therefore, the applicant through concentrated research and discovery, and in line with the spirit of working with perseverance, visualizes " pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis " of the present invention in view of the deficiency that is produced in the known technology eventually, below is brief description of the present invention.

Summary of the invention

In order to overcome the deficiencies in the prior art, the object of the present invention is to provide one group to comprise the raw material of ginsenoside (Rg1+Rb1), glycyrrhizic acid and Fructus Jujubae cAMP, pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis or the health food made, particularly effective component is clear and definite, curative effect is obvious, side effect is low, takes safe new solution for a long time.

The solution of medicine of the present invention is the result who concentrates on studies and explore through me, pathology and pharmacology's theory according to modern medicine treatment melancholia and anxiety neurosis, the particularly drug targets of mechanism of action research behind the bind receptor, prove through a large amount of zooperies: the ginsenoside is contained adenyl cyclase (adenylate cyclase, AC) stimulate adenosine, and contain the inhibition composition of cAMP phosphodiesterase (CAPD); Glycyrrhizic acid (enoxolone) is cAMP phosphodiesterase (CAPD) potent inhibitor; To comprise ginsenoside (Rg1+Rb1), the material combination of glycyrrhizic acid, synergism, can further improve concentration and the activity of interior cAMP of body and PKA, and the concentration of cAMP and increased activity, then can increase norepinephrine (norepinephrine, NE) etc. neurotransmitter synthetic with discharge, strengthen Brain Derived Neurotrophic Factor (brain-derived neurotrophic factor, BDNF) expression, suppress hypothalmus-pituitary-adrenal axis (hypothalamic-pituitary-adrenal axis, the secretion of hyperfunction and glucocorticoid hpa axis), thereby reach significant anti-melancholy function, and the concentration of PKA and increased activity, then scalable GABA is to neuronic inhibitory action, thereby reaches significant anxiety function; In addition, Fructus Jujubae cAMP can participate in the metabolic process of cAMP in the body as exogenous non-hydrolysis class cAMP, but mimic hormone effect, improve the expression of interior cAMP of body and PKA, thereby play anti-melancholy and effect antianxity, therefore, also can will comprise the material combination of ginsenoside (Rg1+Rb1), glycyrrhizic acid and Fructus Jujubae cAMP, further strengthen anti-melancholy of the present invention and effect antianxity.Radix Ginseng, Radix Glycyrrhizae, Fructus Jujubae have been the traditional Chinese medical science and tonic medicated diet medical material and food commonly used since several thousand, in edible and clinical use in 1,100, fully prove the safety of Radix Ginseng, Radix Glycyrrhizae, Fructus Jujubae compatibility.Inventor research and result of experiment prove: these three kinds of medical materials do not possess significant anti-melancholy and anxiety curative effect if only being used for the treatment of the main flow medicine of melancholia and anxiety neurosis in the extract that extracts gained with general known decoction method and the prior art compares; The inventor is further purified the pharmaceutical composition made from after the concentration that improves active ingredients such as ginsenoside (Rg1+Rb1), glycyrrhizic acid and Fructus Jujubae cAMP contained in the extract with the extract of three kinds of medical materials, the main flow medicine paroxetine (Paroxetine) and the diazepam (Diazepam) that are used for the treatment of melancholia and anxiety neurosis in result of experiment proof and the prior art are compared, and have significant anti-melancholy and anxiety curative effect; Collect behind three kinds of medicinal material extract and the purification extract obtained outside remaining residue, though detect ginsenoside Rg1, Rb1, glycyrrhizic acid and the Fructus Jujubae cAMP that the back contains trace, do not have significant anti-melancholy and anxiety function through proving behind the animal experiment.And take Radix Ginseng, Radix Glycyrrhizae and Fructus Jujubae the side effect after the anti-melancholy and anxiety main flow drug administration in the aforementioned known techniques can not take place, sufferer is interrupted because fearing side effect never again or is refused Drug therapy.So the inventor proposes to comprise the raw material of ginsenoside (Rg1+Rb1), glycyrrhizic acid and Fructus Jujubae cAMP, make the oral drugs or the health food that are used for the treatment of melancholia and anxiety neurosis, particularly effective component is clear and definite, curative effect is obvious, side effect is low, takes safe new solution for a long time to improve the deficiency that is produced in the known technology.

Because being converted into the conversion ratio of enoxolone in vivo, glycyrrhizic acid almost reaches 100%, and the fat-soluble enoxolone stronger than glycyrrhizic acid can enter in the brain through blood brain barrier, so suppressing CAPD, glycyrrhizic acid undertaken by being converted into enoxolone in the body, therefore, can be that raw material is made pharmaceutical composition of the present invention with glycyrrhizic acid or enoxolone.

The present invention has disclosed the pharmaceutical composition of a kind of melancholia of being used for the treatment of and anxiety neurosis, and it is to comprise that by Radix Ginseng and Radix Glycyrrhizae be that raw material is made.

Preferably, pharmaceutical composition of the present invention is to comprise that by the described Radix Ginseng of 4～60 weight portions and the described Radix Glycyrrhizae of 2～30 weight portions be that raw material is made.

Preferably, pharmaceutical composition of the present invention is to comprise that by the described Radix Ginseng of 10～28 weight portions and the described Radix Glycyrrhizae of 5～14 weight portions be that raw material is made.

According to a further aspect in the invention, the present invention has disclosed the pharmaceutical composition of a kind of melancholia of being used for the treatment of and anxiety neurosis, and it is to comprise by Radix Ginseng, Radix Glycyrrhizae and Fructus Jujubae being that raw material is made.

Preferably, pharmaceutical composition of the present invention is to comprise that by the described Radix Ginseng of 4～60 weight portions, the described Radix Glycyrrhizae of 2～30 weight portions and the described Fructus Jujubae of 2～40 weight portions be that raw material is made.

Preferably, pharmaceutical composition of the present invention is to comprise that by the described Radix Ginseng of 10～28 weight portions, the described Radix Glycyrrhizae of 5～14 weight portions and the described Fructus Jujubae of 4～18 weight portions be that raw material is made.

According to a further aspect in the invention, the present invention has disclosed the pharmaceutical composition of a kind of melancholia of being used for the treatment of and anxiety neurosis, it be comprise by the raw material that contains ginsenoside Rg1, Rb1 and glycyrrhizic acid or enoxolone made.

Preferably, pharmaceutical composition of the present invention is to comprise by containing ginsenoside (Rg1+Rb1) adding up to the raw material of 2～25 weight portions and glycyrrhizic acid or enoxolone 3～46 weight portions made.

Preferably, pharmaceutical composition of the present invention is to comprise by containing ginsenoside (Rg1+Rb1) adding up to the raw material of 4～12 weight portions and glycyrrhizic acid or enoxolone 5～15 weight portions made.

Preferably, pharmaceutical composition of the present invention comprise that described ginsenoside is the Radix Ginseng extract that contains ginsenoside Rg1 and Rb1, and described Radix Glycyrrhizae acids is the Radix Glycyrrhizae extract that contains glycyrrhizic acid.

According to a further aspect in the invention, the present invention has disclosed the pharmaceutical composition of a kind of melancholia of being used for the treatment of and anxiety neurosis, it be comprise by the raw material that contains ginsenoside Rg1, Rb1 and glycyrrhizic acid or enoxolone and Fructus Jujubae cAMP made.

Preferably, pharmaceutical composition of the present invention, be comprise by the raw material of the Fructus Jujubae cAMP of the glycyrrhizic acid that contains the ginsenoside (Rg1+Rb1) that adds up to 2～25 weight portions and 3～46 weight portions or enoxolone and 0.002～0.4 weight portion made.

Preferably, pharmaceutical composition of the present invention, be comprise by the raw material of the Fructus Jujubae cAMP of the glycyrrhizic acid that contains the ginsenoside (Rg1+Rb1) that adds up to 4～12 weight portions and 5～15 weight portions or enoxolone and 0.01～0.08 weight portion made.

Preferably, pharmaceutical composition of the present invention, comprise that described ginsenoside is the Radix Ginseng extract that contains ginsenoside Rg1 and Rb1, described Radix Glycyrrhizae acids is the Radix Glycyrrhizae extract that contains glycyrrhizic acid, and described Fructus Jujubae cyclic adenosine monophosphate is the Fructus Jujubae extract that contains Fructus Jujubae cyclic adenosine monophosphate.

Preferably, pharmaceutical composition of the present invention, the wherein said raw material that contains Fructus Jujubae cyclic adenosine monophosphate is following second extract: extract Fructus Jujubae earlier and obtain first extract, described first extract of repurity gets described second extract, and the Fructus Jujubae cyclic adenosine monophosphate concentration of wherein said second extract is higher than the Fructus Jujubae cyclic adenosine monophosphate concentration of described first extract.

Preferably, pharmaceutical composition of the present invention can contain and is selected from a kind of in pharmaceutically acceptable carrier, additive and the combination thereof.

Preferably, pharmaceutical composition of the present invention can be made a dosage form, and described dosage form is selected from any in the oral Pharmaceutical dosage forms on lozenge, capsule, powder, tablet, powder, solution, microcapsule, suspensoid, Emulsion, granule, drop pill, pill and the pharmaceutics.

Preferably, described pharmaceutical composition can be used to make medicine, health food and the nutrient that is used for the treatment of depression.

According to a further aspect in the invention, the present invention has disclosed the pharmaceutical composition of a kind of melancholia of being used for the treatment of and anxiety neurosis, and the wherein said preparation method that contains the raw material of Fructus Jujubae cyclic adenosine monophosphate comprises the following steps:

(a) extract Fructus Jujubae and obtain first extract; And

(b) described first extract of purification obtains second extract,

The Fructus Jujubae cyclic adenosine monophosphate concentration of wherein said second extract is higher than the Fructus Jujubae cyclic adenosine monophosphate concentration of described first extract.

Preferably, described preparation method, wherein step (b) is used the Fructus Jujubae cyclic adenosine monophosphate in described first extract of macroporous resin upper prop adsorbing separation that contains aldehyde radical.

Preferably, described preparation method, wherein step (b) is selected the Fructus Jujubae cyclic adenosine monophosphate in described first extract of macroporous resin OU-2 upper prop adsorbing separation that contains aldehyde radical for use.

Preferably, described preparation method, wherein step (b) is separated Fructus Jujubae cyclic adenosine monophosphate in described first extract with macroporous resin ME-2 upper prop again.

The pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis described in description of the present invention and the claim, it is the core content of realizing the object of the invention, after the present invention is open, those skilled in the art can be according to theory of Chinese medical science or relevant modern pharmacology theory, said medicine is carried out conventional adding simplify and cut out or alternative with pharmaceutically active ingredient (as Radix Polygalae glycoside, saikoside, glycycoumarin etc.) in identical other of efficacy effect.The adding of this routine simplifies cuts out and with the Chinese medicine of other similar or identical CAPD inhibitor of effect mechanism, AC activator or effective ingredient substitutes accordingly; all belong to the general technical activity of art technology and research worker, so it is all within protection scope of the present invention.

The present invention obtains preferable understanding by consulting accompanying drawing and detailed description.

The accompanying drawing summary

Fig. 1 is the method flow sketch map of the preparation embodiment of the invention 1 medicine.

Fig. 2 is the method flow sketch map of the preparation embodiment of the invention 2 medicines.

Fig. 3 is the method flow sketch map of the preparation embodiment of the invention 3 medicines.

Fig. 4 is the method flow sketch map of the preparation embodiment of the invention 4 medicines.

Fig. 5 is the method flow sketch map of the preparation embodiment of the invention 5 medicines.

Fig. 6 is the method flow sketch map of the preparation embodiment of the invention 6 medicines.

The specific embodiment

Further specify the present invention below with reference to drawings and Examples.The present invention adopts method known to those skilled in the art to prepare medicine of the present invention in conjunction with feature of the present invention.Following examples only are in order to illustrate, and non-limiting the present invention.

In order to finish purpose of the present invention, the present invention proposes following technical proposal especially.

The present invention has disclosed the pharmaceutical composition of a kind of melancholia of being used for the treatment of and anxiety neurosis, and it is made by the raw material that contains ginsenoside (Rg1+Rb1), glycyrrhizic acid and Fructus Jujubae cAMP.

Scheme one:

To comprise that Radix Ginseng and Radix Glycyrrhizae are that raw material is made the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis.

Scheme two:

With the described Radix Ginseng that comprises 4～60 weight portions and the described Radix Glycyrrhizae of 2～30 weight portions is that raw material is made the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis.

Scheme three:

With the described Radix Ginseng that comprises 10～28 weight portions and the described Radix Glycyrrhizae of 5～14 weight portions is that raw material is made the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis.

Scheme four:

To comprise that Radix Ginseng, Radix Glycyrrhizae and Fructus Jujubae are that raw material is made the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis.

Scheme five:

With the described Radix Ginseng that comprises 4～60 weight portions, the described Radix Glycyrrhizae of 2～30 weight portions and the described Fructus Jujubae of 2～40 weight portions is that raw material is made the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis.

Scheme six:

With the described Radix Ginseng that comprises 10～28 weight portions, the described Radix Glycyrrhizae of 5～14 weight portions and the described Fructus Jujubae of 4～18 weight portions is that raw material is made the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis.

Scheme seven:

Make the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis to comprise the raw material that contains ginsenoside Rg1, Rb1 and glycyrrhizic acid or enoxolone.

Scheme eight:

To comprise that containing the ginsenoside (Rg1+Rb1) who adds up to 2～25 weight portions makes pharmaceutical composition of the present invention with the glycyrrhizic acid of 3～46 weight portions or the raw material of enoxolone.

Scheme nine:

To comprise that containing the ginsenoside (Rg1+Rb1) who adds up to 4～12 weight portions makes pharmaceutical composition of the present invention with the glycyrrhizic acid of 5～15 weight portions or the raw material of enoxolone.

Scheme ten:

To comprise that Radix Ginseng extract that contains aforementioned weight ginsenoside (Rg1+Rb1) and the Radix Glycyrrhizae extract that contains the aforementioned weight glycyrrhizic acid are that raw material is made pharmaceutical composition of the present invention.

Scheme 11:

Make the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis to comprise the raw material that contains ginsenoside Rg1, Rb1, glycyrrhizic acid or enoxolone and Fructus Jujubae cAMP.

Scheme 12:

Raw material with the Fructus Jujubae cAMP that comprises the glycyrrhizic acid that contains the ginsenoside (Rg1+Rb1) that adds up to 2～25 weight portions, 3～46 weight portions or enoxolone and 0.002～0.4 weight portion is made pharmaceutical composition of the present invention.

Scheme 13:

Raw material with the Fructus Jujubae cAMP that comprises the glycyrrhizic acid that contains the ginsenoside (Rg1+Rb1) that adds up to 4～12 weight portions, 5～15 weight portions or enoxolone and 0.01～0.08 weight portion is made pharmaceutical composition of the present invention.

Scheme 14:

To comprise that the Radix Ginseng extract that contains aforementioned weight ginsenoside (Rg1+Rb1) and the Fructus Jujubae extract that contains the Radix Glycyrrhizae extract of aforementioned weight glycyrrhizic acid and contain aforementioned weight Fructus Jujubae cAMP are that raw material is made pharmaceutical composition of the present invention.

Scheme 15:

Pharmaceutical composition of the present invention, the wherein said raw material that contains Fructus Jujubae cyclic adenosine monophosphate is to be that raw material is made pharmaceutical composition of the present invention with following second extract: extract Fructus Jujubae earlier and obtain first extract, described first extract of repurity gets described second extract, and the Fructus Jujubae cyclic adenosine monophosphate concentration of wherein said second extract is higher than the Fructus Jujubae cyclic adenosine monophosphate concentration of described first extract.

Scheme 16:

Pharmaceutical composition of the present invention, the wherein said preparation method that contains the raw material of Fructus Jujubae cyclic adenosine monophosphate comprises the following steps:

(a) extract Fructus Jujubae and obtain first extract; And

(b) described first extract of purification obtains second extract, and the Fructus Jujubae cyclic adenosine monophosphate concentration of described second extract is higher than the Fructus Jujubae cyclic adenosine monophosphate concentration of described first extract.

Scheme 17:

Aforesaid preparation method, wherein step (b) is selected the Fructus Jujubae cyclic adenosine monophosphate in described first extract of macroporous resin upper prop adsorbing separation that contains aldehyde radical for use.

Scheme 18:

Aforesaid preparation method, wherein step (b) is selected the Fructus Jujubae cyclic adenosine monophosphate in described first extract of macroporous resin OU-2 upper prop adsorbing separation that contains aldehyde radical for use.

Scheme 19:

Aforesaid preparation method, wherein step (b) is separated Fructus Jujubae cyclic adenosine monophosphate in described first extract with macroporous resin ME-2 upper prop again.

Scheme 20:

Pharmaceutical composition of the present invention can contain pharmaceutically acceptable carrier, additive or its combination.

Scheme 21:

Pharmaceutical composition of the present invention can be made a dosage form, and described dosage form is selected from any in the oral Pharmaceutical dosage forms on lozenge, capsule, powder, tablet, powder, solution, microcapsule, suspensoid, Emulsion, granule, drop pill, pill and the pharmaceutics.

Scheme 22:

Pharmaceutical composition of the present invention can be used to make medicine, health food and the nutrient that is used for the treatment of melancholia and anxiety neurosis.

In order to finish purpose of the present invention, the special manufacture method that proposes following medicine.

Method one:

To comprise that the described Radix Ginseng of 4～60 weight portions and the described Radix Glycyrrhizae of 2～30 weight portions are raw material, must contain the extract of ginsenoside Rg1, Rb1 and glycyrrhizic acid behind extraction and the purification, it is processed into the pharmaceutical composition that the present invention is used for the treatment of melancholia and anxiety neurosis.

Method two:

To comprise that the described Radix Ginseng of 10～28 weight portions and the described Radix Glycyrrhizae of 5～14 weight portions are raw material, must contain the extract of ginsenoside Rg1, Rb1 and glycyrrhizic acid behind extraction and the purification, it is processed into the pharmaceutical composition that the present invention is used for the treatment of melancholia and anxiety neurosis.

Method three:

To comprise that the described Radix Ginseng of 4～60 weight portions, the described Radix Glycyrrhizae of 2～30 weight portions and the described Fructus Jujubae of 2～40 weight portions are raw material, must contain the extract of ginsenoside Rg1, Rb1, glycyrrhizic acid and Fructus Jujubae cAMP behind extraction and the purification, it is processed into the pharmaceutical composition that the present invention is used for the treatment of melancholia and anxiety neurosis.

Method four:

To comprise that the described Radix Ginseng of 10～28 weight portions, the described Radix Glycyrrhizae of 5～14 weight portions and the described Fructus Jujubae of 4～18 weight portions are raw material, must contain the extract of ginsenoside Rg1, Rb1, glycyrrhizic acid and Fructus Jujubae cAMP behind extraction and the purification, it is processed into the pharmaceutical composition that the present invention is used for the treatment of melancholia and anxiety neurosis.

Method five:

The extract that contains ginsenoside Rg1, Rb1 and glycyrrhizic acid of extraction and purification is a raw material in Radix Ginseng and Radix Glycyrrhizae, or the direct raw material that contains ginsenoside Rg1, Rb1 and glycyrrhizic acid or enoxolone that has been prepared into of employing, be processed into the pharmaceutical composition that the present invention is used for the treatment of melancholia and anxiety neurosis.

Method six:

To contain the ginsenoside (Rg1+Rb1) and the glycyrrhizic acid of 3～46 weight portions or the raw material of enoxolone that add up to 2～25 weight portions, be processed into pharmaceutical composition of the present invention.

Method seven:

To contain the ginsenoside (Rg1+Rb1) and the glycyrrhizic acid of 5～15 weight portions or the raw material of enoxolone that add up to 4～12 weight portions, be processed into pharmaceutical composition of the present invention.

Method eight:

The extract that contains ginsenoside Rg1, Rb1, glycyrrhizic acid and Fructus Jujubae cAMP of extraction and purification is a raw material in Radix Ginseng and Radix Glycyrrhizae and Fructus Jujubae, or the direct raw material that contains ginsenoside Rg1, Rb1, glycyrrhizic acid or enoxolone and Fructus Jujubae cAMP that has been prepared into of employing, be processed into the pharmaceutical composition that the present invention is used for the treatment of melancholia and anxiety neurosis.

Method nine:

To contain the raw material of the Fructus Jujubae cAMP of the glycyrrhizic acid of the ginsenoside (Rg1+Rb1) that adds up to 2～25 weight portions, 3～46 weight portions or enoxolone and 0.002～0.4 weight portion, be processed into pharmaceutical composition of the present invention.

Method ten:

To contain the raw material of the Fructus Jujubae cAMP of the glycyrrhizic acid of the ginsenoside (Rg1+Rb1) that adds up to 4～12 weight portions, 5～15 weight portions or enoxolone and 0.01～0.08 weight portion, be processed into pharmaceutical composition of the present invention.

Method 11:

(a) extract Fructus Jujubae and obtain first extract; And

Method 12:

Method 13:

Method 14:

Method 15:

Method 16:

Pharmaceutical composition of the present invention is made a dosage form, and described dosage form is selected from any in the oral Pharmaceutical dosage forms on lozenge, capsule, powder, tablet, powder, solution, microcapsule, suspensoid, Emulsion, granule, drop pill, pill and the pharmaceutics.

Method 17:

With the method for raw material of the present invention, be processed into medicine, health food and nutrient that the present invention is used for the treatment of melancholia and anxiety neurosis according to GMP pharmaceutical standards and health food manufacturing standard.

Specific embodiment

Further specify the present invention below with reference to accompanying drawing and concrete case study on implementation.

Embodiment 1

See also Fig. 1, be the method flow sketch map of the preparation embodiment of the invention 1 medicine.In Fig. 1, earlier with after the Radix Ginseng fragmentation of 20kg with the extraction of heating of 70% alcoholic solution, through last column chromatographic isolation and purification, drying, must contain 120g ginsenoside's (Rg1+Rb1) Radix Ginseng extract 0.8kg; Then, again with soak at room temperature after the Radix Glycyrrhizae fragmentation of 10kg 12 hours, with decoction and alcohol sedimentation technique extract, concentrate drying, must contain the Radix Glycyrrhizae extract 2kg of glycyrrhizic acid 200g; Afterwards, after Radix Ginseng extract 150g that said method is obtained and Radix Glycyrrhizae extract 200g pulverize mix homogeneously, 350g (containing 22.5g ginsenoside Rg1+Rb1 and 20g glycyrrhizic acid) pharmaceutical composition of the present invention.

Embodiment 2

See also Fig. 2, be the method flow sketch map of the preparation embodiment of the invention 2 medicines.In Fig. 2, be after the Radix Ginseng extract 200g of 96% enoxolone 3.96g and embodiment 1 gained pulverizes mix homogeneously with being prepared into purity, 203.96g (containing 30g ginsenoside Rg1+Rb1 and 3.8g enoxolone) pharmaceutical composition of the present invention.

Embodiment 3

See also Fig. 3, be the method flow sketch map of the preparation embodiment of the invention 3 medicines.In Fig. 3, with the 3.4g purity that has been prepared into is that 90% ginsenoside Rg1,7.8g purity are that 90% ginsenoside Rb1 and 36.8g purity are after 95% glycyrrhizic acid is pulverized mix homogeneously, 48g (containing 10g ginsenoside Rg1+Rb1 and 35g glycyrrhizic acid) pharmaceutical composition of the present invention.

Embodiment 4

See also Fig. 4, be the method flow sketch map of the preparation embodiment of the invention 4 medicines.In Fig. 4, add the water soak at room temperature after the Fructus Jujubae fragmentation with 10kg, extract with decoction and alcohol sedimentation technique again and obtain the Fructus Jujubae extracting solution, reuse macroporous resin OU-2, the successively continuous upper prop adsorbing separation of ME-2 two posts, drying, the Fructus Jujubae extract 30g that must contain Fructus Jujubae cAMP 0.3g supplies preparation medicine of the present invention as raw material.

Then, after Radix Ginseng extract 150g, Radix Glycyrrhizae extract 200g that embodiment 1 is obtained and aforementioned Fructus Jujubae extract 3g pulverize mix homogeneously, 353g (containing 22.5g ginsenoside Rg1+Rb1,20g glycyrrhizic acid and 0.03g Fructus Jujubae cAMP) pharmaceutical composition of the present invention.

Embodiment 5

See also Fig. 5, be the method flow sketch map of the preparation embodiment of the invention 5 medicines.In Fig. 5, after the Fructus Jujubae extract 0.5g that Radix Ginseng extract 150g that embodiment 1 is obtained and Radix Glycyrrhizae extract 200g and embodiment 4 obtain pulverizes mix homogeneously, 350.5g (containing 22.5g ginsenoside Rg1+Rb1,20g glycyrrhizic acid and 0.005g Fructus Jujubae cAMP) pharmaceutical composition of the present invention.

Embodiment 6

See also Fig. 6, be the method flow sketch map of the preparation embodiment of the invention 6 medicines.In Fig. 6, with the 6.8g purity that has been prepared into is that 90% ginsenoside Rg1,15.6g purity are that 90% ginsenoside Rb1,26g purity are after Fructus Jujubae extract 10g that 96% enoxolone and embodiment 4 obtain pulverizes mix homogeneously, 58.4g (containing 20g ginsenoside Rg1+Rb1,25g enoxolone and 0.1g Fructus Jujubae cAMP) pharmaceutical composition of the present invention.

The influence of 1 pair of mouse tail suspension experiment of experimental example one embodiment

1.1 laboratory animal

The ICR mice, male, body weight 22.0 ± 2g, secondary, the department of the Chinese Academy of Sciences of laboratory animal section of Beijing Capital University of Medical Sciences provides.

1.2 experimental drug

Embodiment 1: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.

Paroxetine (seroxat): Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.

1.3 experimental apparatus: stopwatch.

1.4 dosage design

Embodiment 1 heavy dose: 80mg/kg/d, middle dosage: 40mg/kg/d and low dose: 20mg/kg/d.

1.5 experimental technique and result

1.5.1 grouping administration

With the mice random packet, 10 every group: 1. embodiment 1 heavy dose is organized (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 1; 3. embodiment 1 small dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. normal saline group (PO).Hang tail in 1 hour after the last administration tests.

1.5.2 experimental technique

Mouse tail (apart from tail point 1cm place) is bonded at head height with adhesive plaster on the batten of table top 5cm, suspended in midair 6 minutes, write down the dead time of mice in back 5 minutes.

1.5.3 statistical procedures

Experimental data represents that with X ± SD experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.

1.5.4 experimental result

Experimental result sees also table 1.

The influence of table 1,1 pair of mice dead time of embodiment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

According to above experiment, the embodiment of the invention 1 big or middle dosage group and paroxetine group all can reduce the dead time after the mouse tail suspension as can be seen, and compared significant difference with normal saline group (model group), thereby can infer that the embodiment of the invention 1 has the depressed function of anti-experimental character.

The influence that 1 pair of mice reserpine induction of experimental example two embodiment body temperature descends

2.1 laboratory animal

2.2 experimental drug

Reserpine: Guangdong Bangmin Pharmaceutical Co., Ltd..

2.3 experimental apparatus

GM222 type electronic thermometer, stopwatch.

2.4 dosage design

2.5 experimental technique and result

2.5.1 grouping administration

With the mice random packet, 10 every group: 1. embodiment 1 heavy dose is organized (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 1; 3. embodiment 1 small dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. normal saline group (PO).

2.5.2 experimental technique

After administration in the 8th day, measured mice anus temperature in 1 hour,, behind the injection reserpine, measured mice anus temperature in 4 hours more then through lumbar injection reserpine 2mg/kg.The degree of depth and time homogeneous that each thermometric chronothermometer inserts the mice anus cause.

2.5.3 statistical procedures

2.5.4 experimental result

Experimental result sees also table 2.

The influence that table 2, embodiment 1 mice reserpine induction body temperature descend

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

According to above experiment, the embodiment of the invention 1 large, medium and small three dosage groups and paroxetine group all can obviously reduce the body temperature decline of reserpine induction as can be seen, show that the depressed effect of its anti-experimental character may be with influence monoamine neurotransmitter content relevant, thereby can infer that the embodiment of the invention 1 has anti-experimental character depression function.

1 pair of mice light and shade of experimental example three embodiment is worn the influence of case experiment

3.1 laboratory animal

Kunming mouse, male, body weight 24-26g, secondary is provided by the department of the Chinese Academy of Sciences of Department Of Medicine, Peking University's laboratory animal section.

3.2 experimental drug

Diazepam (Diazepam): Tianjin gold brightness aminoacid company limited product.

3.3 experimental apparatus: the self-control light and shade is worn case.

3.4 dosage design

3.5 experimental technique and result

3.5.1 grouping administration

Mice is divided into 5 groups at random, 10 every group: 1. embodiment 1 heavy dose is organized (80mg/kg/d); 2. dosage group (40mg/kg/d) among the embodiment 1; 3. embodiment 1 small dose group (20mg/kg/d); 4. diazepam group (2.5mg/kg/d); 5.NS group.Gastric infusion once a day, successive administration 7 days, animal ad lib drinking-water was tested after after the administration in the 8th day 1 hour during the administration.

3.5.2 experimental technique

The experiment of mice light and shade case: light and shade is worn the middle camera bellows of case (44cm x 21cm x 21cm) and is accounted for 1/3, and add a cover at the top; Camera-lucida accounts for 2/3, and the light illumination has a door opening to pass for animal between two the casees.During experiment mice placed camera-lucida central authorities, the back of the body is towards camera bellows, observes and writes down mice in 10 minutes and enter the number of times that returns bright chamber behind the darkroom.And with this index as evaluation medicine angst resistance effect.

3.5.3 statistical procedures

Experimental data represents that with X ± SD experimental result is carried out one factor analysis of variance with SPSS 11.5 statistical softwares.

3.5.4 experimental result

Experimental result sees also table 3.

The influence that the case number of times is worn in table 3, the experiment of 1 pair of mice light and shade of embodiment case

Annotate: ^*P＜0.05, ^*Compare with the NS group P＜0.01

3.6 explanation

The experiment of light and shade case that this experiment is adopted is to be based upon muroid to the congenital detest of high light with on the basis of the spontaneous exploratory behavior of new environment, and the effect that can be used for treating the medicine of human anxiety neurosis and they can promote mice on this model spontaneous exploratory behavior clinically increases has good dependency.Show that according to above experimental result embodiment 1 large, medium and small dosage group and diazepam group all can significantly increase mice and return bright chamber number of times by the darkroom, have statistical significance with NS group comparing difference.Experimental result proof embodiment 1 has angst resistance effect.

3.7 conclusion

Show that according to above experimental result the embodiment of the invention 1 large, medium and small dosage group and diazepam group all can significantly increase mice and return bright chamber number of times by the darkroom, show that embodiment 1 has angst resistance effect.

The influence of 2 pairs of mouse tail suspension experiments of experimental example four embodiment

4.1 laboratory animal

4.2 experimental drug

Embodiment 2: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.

4.3 experimental apparatus

Stopwatch.

4.4 dosage design

Embodiment 2 heavy doses: 80mg/kg/d, middle dosage: 40mg/kg/d and low dose: 20mg/kg/d.

4.5 experimental technique and result

4.5.1 grouping administration

With the mice random packet, 10 every group: 1. embodiment 2 heavy doses are organized (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 2; 3. embodiment 2 small dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. normal saline group (PO).Hang tail in 1 hour after the last administration tests.

4.5.2 experimental technique

4.5.3 statistical procedures

4.5.4 experimental result

Experimental result sees also table 4.

The influence of table 4,2 pairs of mice dead times of embodiment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

According to above experiment, dosage group and paroxetine group all can reduce dead time after the mouse tail suspension in the embodiment of the invention 2 as can be seen, and compared significant difference with normal saline group (model group), thereby can infer that the embodiment of the invention 2 has the depressed function of anti-experimental character.

The influence that 2 pairs of mice reserpine inductions of experimental example five embodiment body temperature descends

5.1 laboratory animal

5.2 experimental drug

Reserpine: Guangdong Bangmin Pharmaceutical Co., Ltd..

5.3 experimental apparatus

GM222 type electronic thermometer, stopwatch.

5.4 dosage design

5.5 experimental technique and result

5.5.1 grouping administration

With the mice random packet, 10 every group: 1. embodiment 2 heavy doses are organized (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 2; 3. embodiment 2 small dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. normal saline group (PO).

5.5.2 experimental technique

5.5.3 statistical procedures

5.5.4 experimental result

Experimental result sees also table 5.

The influence that table 5, embodiment 2 mice reserpine induction body temperature descend

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

According to above experiment, the body temperature that dosage group and paroxetine group all can obviously reduce reserpine induction in the embodiment of the invention 2 descends as can be seen, show that the depressed effect of its anti-experimental character may be with influence monoamine neurotransmitter content relevant, thereby can infer that the embodiment of the invention 2 has anti-experimental character depression function.

The influence of 3 pairs of mouse tail suspension experiments of experimental example six embodiment

6.1 laboratory animal

6.2 experimental drug

Embodiment 3: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.

6.3 experimental apparatus:

Stopwatch.

6.4 dosage design

Embodiment 3 heavy doses: 80mg/kg/d, middle dosage: 40mg/kg/d and low dose: 20mg/kg/d.

6.5 experimental technique and result

6.5.1 grouping administration

With the mice random packet, 10 every group: 1. embodiment 3 heavy doses are organized (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 3; 3. embodiment 3 small dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. normal saline group (PO).Hang tail in 1 hour after the last administration tests.

6.5.2 experimental technique

6.5.3 statistical procedures

6.5.4 experimental result

Experimental result sees also table 6.

The influence of table 6,3 pairs of mice dead times of embodiment

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

According to above experiment, the embodiment of the invention 3 big or middle dosage groups and paroxetine group all can reduce the dead time after the mouse tail suspension as can be seen, and compared significant difference with normal saline group (model group), thereby can infer that the embodiment of the invention 3 has the depressed function of anti-experimental character.

The influence that 3 pairs of mice reserpine inductions of experimental example seven embodiment body temperature descends

7.1 laboratory animal

7.2 experimental drug

Reserpine: Guangdong Bangmin Pharmaceutical Co., Ltd..

7.3 experimental apparatus

GM222 type electronic thermometer, stopwatch.

7.4 dosage design

7.5 experimental technique and result

7.5.1 grouping administration

With the mice random packet, 10 every group: 1. embodiment 3 heavy doses are organized (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 3; 3. embodiment 3 small dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. normal saline group (PO).

7.5.2 experimental technique

7.5.3 statistical procedures

7.5.4 experimental result

Experimental result sees also table 7.

The influence that table 7, embodiment 3 mice reserpine induction body temperature descend

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

According to above experiment, the embodiment of the invention 3 large, medium and small dosage groups and paroxetine group all can obviously reduce the body temperature decline of reserpine induction as can be seen, show that the depressed effect of its anti-experimental character may be with influence monoamine neurotransmitter content relevant, thereby can infer that the embodiment of the invention 3 has anti-experimental character depression function.

The influence of 4 pairs of rat olfactory bulb damages of experimental example eight embodiment experiment

8.1 laboratory animal

Olfactory bulb is damaged model: healthy Wistar male rat, and secondary, body weight 330 ± 20g purchases in Beijing Vital River Experimental Animals Technology Co., Ltd. (quality certification numbering SCXK (capital) 2002-0003).

8.2 reagent and medicine

Embodiment 4 provides (lot number: 060313) by Ou Naer biotechnology company limited, paroxetine is that (lot number: 04050011), above medicine uses for irritating stomach with 0.5% Sodium Tvlose (CMC-Na) preparation back Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product; Benzylpenicillin sodium for injection is Huabei Pharmaceutic Co., Ltd's product (lot number: S0511204); Norepinephrine (NE) and 5-hydroxy tryptamine (5-HT) standard substance are Sigma company product; Other reagent is commercially available.

8.3 instrument

Wild experimental box is opened in self-control, keeps away dark experimental box, rat brain stereotaxic instrument, high performance liquid chromatograph, DFM-96 type 10 pipe radioimmunity gamma counters.

8.4 experimental technique

8.4.1 animal grouping and medication

Rat is divided 6 groups at random, dosage group (30mg/kg/d), embodiment 4 low dose group (15mg/kg/d), paroxetine group (2mg/kg/d) among sham operated rats, model control group, embodiment 4 high dose group (60mg/kg/d), the embodiment 4.Prepared with 0.5% Sodium Tvlose (CMC-Na) by reagent and positive drug.Gastric infusion once a day.

8.4.2 model preparation method

Rat is used chloral hydrate anesthesia, anesthesia back from the rat bregma in front of the door 1cm 1cm median line to the anterior fontanelle cut, expose skull.8mm, 2mm place, the median line both sides window that opens seam respectively before the distance anterior fontanelle, the about 2mm of diameter.Vertically inserted intracranial 2 seconds with special electric cautery, destroy olfactory bulb, with styptic sponge used filling bone window, skin suture; (intraperitoneal IP) gives and penicillin sodium 40,000 units/Kg per 4 days of postoperative, and gives continuously and be subjected to the reagent thing 24 days with lumbar injection.

8.5 observation index

8.5.1 open wild experiment

Open wild experimental box and be configured to by light blue plywood and aluminum alloy frame that (1m * 1m * 0.4m), (each 20cm * 20cm), be the periphery lattice along wall, all the other are center lattice to be divided into 25 grids at the bottom of the case.Animal is put into positive medium square, and that observes animal in 3 minutes strides lattice number of times (striding into adjacent lattice more than the three-jaw) and the number of times of standing (more than the liftoff 1cm of two forelimbs).

8.5.2 passive avoidance experiment-darkness avoidance test

Be made up of bright, dark two Room in the experimental box, the centre has a passage to come in and go out for rat, and the darkroom barrier links with the electric shock instrument, and an active clapboard is arranged between two Room.Entering the darkroom as rat is then shocked by electricity.During training, the rat head is put into bright chamber adaptation 5 minutes in the hole dorsad, dividing plate is extracted out observed 5 minutes then, the record rat enters the darkroom time (getting an electric shock incubation period) first, and this is a school grade.Retest after 24 hours, the extraction dividing plate is also switched on and was observed the time that rat pierces the darkroom for the first time in 5 minutes, and this is the memory achievement.

8.6 statistical procedures

8.7 experimental result

See also table 8 8.7.1 open wild experimental result.

Table 8, olfactory bulb are damaged rat model and are opened wild experimental result

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

See also table 9 8.7.2 keep away dark experimental result.

Table 9, olfactory bulb are damaged rat model and are kept away dark experimental result

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

Experimental example eight results show: embodiment can obviously improve olfactory bulb for 4 heavy dose of groups and damage the rat level and the increase that moves both vertically that is caused, and the dosage group is damaged moving both vertically of rat model to olfactory bulb among the embodiment 4 increases the effect that also has clear improvement.In addition, the effect of also having clear improvement that the embodiment 4 big or middle dosage groups rat that damage is caused to olfactory bulb is learnt and memory function goes down.

The unpredictable influence that stress test for a long time of 4 pairs of rats of experimental example nine embodiment

9.1 laboratory animal

The long-term Stress model of unpredictability: healthy Wistar male rat, secondary, body weight 240～270g purchases in Beijing Vital River Experimental Animals Technology Co., Ltd. (quality certification numbering SCXK (capital) 2002-0003).

9.2 reagent and medicine

9.3 instrument

9.4 experimental technique

9.4.1 animal grouping and medication

9.4.2 model preparation method

The long-term Stress model of unpredictability: blank group normal diet drinking-water, do not give any stimulation.Other five groups, every cage is raised 1, and accept 24 days unpredictable stress stimulations, and comprising: 3 fasting in 24 hours, cut off the water supply in 3 times 24 hours, 3 times 24 hours moist bedding and padding (adding water 200ml in the Mus box), 3 illuminations all night, 34 ℃ of cold water swimming 5 minutes, 3 45 ℃ of baking box baking the affected part after applying some drugs 5 minutes, 3 times 1 minute folder tail, and high speed level vibration in 3 times 30 minutes.Give a kind of stimulation every day at random, stimulated altogether 24 days, every kind of stimulation must not give continuously.Gastric infusion once a day, totally 24 days.

9.5 observation index

9.5.1 open wild experiment: the same.

9.5.2 passive avoidance experiment: the same.

9.5.3 rat forced swimming

The experiment branch carried out in two days after the last administration.Prerun in first day 15 minutes is adorned 25 ℃ of warm water, depth of water 25cm in the glass jar.After 24 hours, formally test, after the administration 1 hour, rat is put into cylinder, observe and write down 5 minute dead time.

9.5.4 body weight test

The value added of body weight before and after relatively each treated animal is tested.

9.5.5 drink sucrose water testing:

More various animal sucrose intakes.Allow and respectively organize rat and drink 1% sucrose water (being 1 hour regularly), stress before, stress respectively survey amount of drinking water 3 weeks one time in the back; Rat is prohibited water after 14 hours in fasting, 1% sucrose water is put into cage replace original drinking water.Weighing record rat is drunk the heavy difference of bottle of 1 hour front and back of sucrose water and calculates each sucrose diseases caused by retention of fluid consumption.The difference of sucrose solution intake during relatively each group is tested each time.

9.5.6 high performance liquid chromatogram-electrochemical detection method

Measure NE and 5-HT content in the rat cerebral cortex.

9.6 statistical procedures

9.7 experimental result

9.7.1 rat drink sucrose water yield result sees also table 10.

Table 10, the long-term Stress model rat drink of the unpredictability sucrose water yield

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

9.7.2 the rat body weight incremental result sees also table 11.

Table 11, the long-term Stress model rat body weight of unpredictability increment

Annotate: compare with model group ^*P＜0.01

9.7.3 rat forced swimming experiment dead time result sees also table 12.

Table 12, the long-term Stress model rat of unpredictability forced swimming experiment dead time

Annotate: compare with model group ^*P＜0.05, ^*P＜0.01

9.7.4 rat opens wild experimental result and sees also table 13.

Table 13, the long-term Stress model rat of unpredictability open wild experimental result

Annotate: compare with model group ^*P＜0.05, ^*P＜0.01

9.7.5 rat is kept away dark experimental result and sees also table 14.

Table 14, the long-term Stress model rat of unpredictability are kept away dark experimental result

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

9.7.6 NE and 5-HT content detection result see also table 15 in the rat cerebral cortex.

NE and 5-HT content in table 15, the long-term Stress model rat cerebral cortex of unpredictability

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

Experimental example nine results show: small dose group can obviously be improved minimizing of the drink sucrose water yield and the weight loss that the long-term stress stimulation of unpredictability is caused among the embodiment 4; Embodiment 4 big-and-middle small dose group all can obviously increase the rat forced swimming experiment dead time; Embodiment can obviously improve the rat level and the minimizing that moves both vertically that the long-term stress stimulation of unpredictability is caused for 4 heavy dose of groups, and the rat that embodiment 4 small dose group are caused the long-term stress stimulation of unpredictability moves both vertically and reduces the effect that also has clear improvement; The rat learning capacity that embodiment 4 small dose group are caused the long-term stress stimulation of unpredictability reduces the improvement effect; Embodiment 4 big-and-middle small dose group all can obviously increase NE and 5-HT content in the rat cerebral cortex.

4 pairs of mice light and shades of experimental example ten embodiment are worn the influence of case experiment

10.1 laboratory animal

10.2 experimental drug

Embodiment 4: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.

Diazepam (Diazepam): Tianjin gold brightness aminoacid company limited product.

10.3 experimental apparatus: the self-control light and shade is worn case.

10.4 dosage design

Embodiment 4 heavy doses: 80mg/kg/d, middle dosage: 40mg/kg/d and low dose: 20mg/kg/d.

10.5 experimental technique and result

10.5.1 grouping administration

Mice is divided into 5 groups at random, 10 every group: 1. embodiment 4 heavy doses are organized (80mg/kg/d); 2. dosage group (40mg/kg/d) among the embodiment 4; 3. embodiment 4 small dose group (20mg/kg/d); 4. diazepam group (2.5mg/kg/d); 5.NS group.Gastric infusion once a day, successive administration 7 days, animal ad lib drinking-water was tested after after the administration in the 8th day 1 hour during the administration.

10.5.2 experimental technique

10.5.3 statistical procedures

10.5.4 experimental result

Experimental result sees also table 16.

The influence that the case number of times is worn in table 16, the experiment of 4 pairs of mice light and shades of embodiment case

Annotate: ^*P＜0.05, ^*Compare with the NS group P＜0.01

10.6 explanation

The experiment of light and shade case that this experiment is adopted is to be based upon muroid to the congenital detest of high light with on the basis of the spontaneous exploratory behavior of new environment, and the effect that can be used for treating the medicine of human anxiety neurosis and they can promote mice on this model spontaneous exploratory behavior clinically increases has good dependency.Show that according to above experimental result embodiment 4 large, medium and small dosage groups and diazepam group all can significantly increase mice and return bright chamber number of times by the darkroom, have statistical significance with NS group comparing difference.Experimental result proof embodiment 4 has angst resistance effect.

10.7 conclusion

Show that according to above experimental result the embodiment of the invention 4 large, medium and small dosage groups and diazepam group all can significantly increase mice and return bright chamber number of times by the darkroom, show that embodiment 4 has angst resistance effect.

The influence of 5 pairs of mouse tail suspension experiments of experimental example 11 embodiment

11.1 medicine

Embodiment 5 provides (pilot scale amplification product) by Ou Naer biotechnology company limited; Paroxetine is that (lot number: 05070384), above medicine uses for irritating stomach with normal saline preparation back Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.

11.2 animal

The ICR mice, male, body weight 20.0 ± 1g, secondary is provided by the department of the Chinese Academy of Sciences of Department Of Medicine, Peking University's laboratory animal section, animal quality quality certification SCXK (capital) 2006-0008.

11.3 instrument

Stopwatch.

11.4 method

70 of mices are divided into 5 groups at random, dosage group (40mg/kg/d), embodiment 5 small dose group (20mg/kg/d) among NS group, paroxetine group (3mg/kg/d), embodiment 5 heavy dose of groups (80mg/kg/d), the embodiment 5.Every day gastric infusion once, mice tail end (apart from tail point 1cm place) was bonded on the horizontal supports that places in the open top container with adhesive plaster in 1 hour after administration in the 8th day, makes mice be the state of hanging by the feet, the mice head is about 10cm apart from the bottom surface, suspended in midair 6 minutes, and write down the accumulation dead time of mice in back 5 minutes.

11.5 statistical procedures

11.6 result

Mouse tail suspension experiment dead time result sees also table 17.

The influence of table 17,5 pairs of mouse tail suspension experiment accumulation dead times of embodiment

Annotate: compare with the NS group ^*P＜0.05 ^*P＜0.01

Conclusion:

Result of study shows that embodiment 5 large, medium and small three dosage groups and clinical effective antidepressants paroxetine all can obviously shorten the mouse tail suspension accumulation dead time, shows that embodiment 5 has the depressed effect of certain anti-experimental character.

The influence of 5 pairs of mice forced swimming experiments of experimental example 12 embodiment

12.1 medicine

12.2 animal

12.3 instrument

Stopwatch.

12.4 method

Mice group and administration are tested as mouse tail suspension.Experiment is respectively organized mice and is experimentized after 1 hour in administration, reach mice training swimming in the 8th day 15 minutes before testing, test after 24 hours, mice is put into the glass jar of depth of water 10cm, diameter 14cm respectively, 25 ℃ of water temperatures are observed the 5 minutes record accumulation dead times of mice in water.

12.5 statistical procedures

12.6 result

Mice forced swimming experimental result sees also table 18.

The influence of table 18,5 pairs of mice forced swimming experiments of embodiment

Annotate: compare with the NS group ^*P＜0.05 ^*P＜0.01

Conclusion:

Result of study shows that embodiment 5 large, medium and small dosage groups and clinical effective antidepressants paroxetine all can obviously shorten the mice forced swimming accumulation dead time, shows that embodiment 5 has the depressed effect of certain anti-experimental character.

Experimental example 13

Embodiment 1 and embodiment 4 are extracted last Radix Ginseng residue 9kg, Radix Glycyrrhizae residue 7kg and the Fructus Jujubae residue 0.9kg of back collection, be dried, must contain after the pulverizing, mix homogeneously ginsenoside Rg1, Rb1, and the residue mixture of glycyrrhizic acid and Fructus Jujubae cAMP of denier, carry out controlled trial the influence of mouse tail suspension experiment.

13.1 laboratory animal

13.2 experimental drug

Residue mixture: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.

13.3 experimental apparatus

Stopwatch.

13.4 dosage design

Residue mixture heavy dose: 160mg/kg/d, middle dosage: 80mg/kg/d reach, low dose: 40mg/kg/d.

13.5 experimental technique and result

13.5.1 grouping administration

With the mice random packet, 10 every group: 1. the residue mixture heavy dose is organized (160mg/kg, PO, administration 7d); 2. dosage group (80mg/kg, PO, administration 7d) in the residue mixture; 3. residue mixture small dose group (40mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. normal saline group (PO).Hang tail in 1 hour after the last administration tests.

13.5.2 experimental technique

13.5.3 statistical procedures

13.5.4 experimental result

Experimental result sees also table 19.

Table 19, residue mixture are to the influence of mice dead time

Annotate: compare with model group ^*P＜0.05 ^*P＜0.01

Conclusion:

According to above experiment, though large, medium and small three the dosage groups of residue mixture can shorten the dead time after the mouse tail suspension as can be seen, do not have significance but compare difference, thereby can infer that described residue mixture does not have the depressed function of anti-experimental character with normal saline group (model group).

The present invention is used for the treatment of the range of application of the pharmaceutical composition of melancholia and anxiety neurosis:

1. in the pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis of the present invention, can contain acceptable additive on the materia medica;

2. the pharmaceutical composition of melancholia of being used for the treatment of of the present invention and anxiety neurosis can be processed into it various known dosage forms such as powder, capsule, tablet; And

3. the pharmaceutical composition of melancholia of being used for the treatment of of the present invention and anxiety neurosis can be made the health food that is used for the treatment of melancholia and anxiety neurosis.

The present invention can make multiple change by those skilled in the art, but does not break away from claims scope required for protection.

Claims

1. a pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis comprises that by Radix Ginseng and Radix Glycyrrhizae be that raw material is made.

2. pharmaceutical composition as claimed in claim 1, wherein said pharmaceutical composition comprise that the described Radix Glycyrrhizae by the described Radix Ginseng of 4～60 weight portions and 2～30 weight portions is that raw material is made.

3. pharmaceutical composition as claimed in claim 2, wherein said pharmaceutical composition comprise that also the described Radix Glycyrrhizae by the described Radix Ginseng of 10～28 weight portions and 5～14 weight portions is that raw material is made.

4. pharmaceutical composition as claimed in claim 1, wherein said pharmaceutical composition contain pharmaceutically acceptable carrier, additive or its combination.

5. pharmaceutical composition as claimed in claim 1, wherein said pharmaceutical composition is made a dosage form, described dosage form be selected from lozenge, capsule, powder, tablet, powder, solution, microcapsule, suspensoid, Emulsion, granule, drop pill, pill and the pharmaceutics oral Pharmaceutical dosage forms one of them.

6. pharmaceutical composition as claimed in claim 1, wherein said pharmaceutical composition is made health food or nutrient.

7. a pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis comprises by Radix Ginseng, Radix Glycyrrhizae and Fructus Jujubae being that raw material is made.

8. pharmaceutical composition as claimed in claim 7, wherein said pharmaceutical composition comprise that the described Fructus Jujubae by the described Radix Glycyrrhizae of the described Radix Ginseng of 4～60 weight portions, 2～30 weight portions and 2～40 weight portions is that raw material is made.

9. pharmaceutical composition as claimed in claim 8, wherein said pharmaceutical composition comprise that also the described Fructus Jujubae by the described Radix Glycyrrhizae of the described Radix Ginseng of 10～28 weight portions, 5～14 weight portions and 4～18 weight portions is that raw material is made.

10. pharmaceutical composition as claimed in claim 7, wherein said pharmaceutical composition contain pharmaceutically acceptable carrier, additive or its combination.

11. pharmaceutical composition as claimed in claim 7, wherein said pharmaceutical composition is made a dosage form, described dosage form be selected from lozenge, capsule, powder, tablet, powder, solution, microcapsule, suspensoid, Emulsion, granule, drop pill, pill and the pharmaceutics oral Pharmaceutical dosage forms one of them.

12. pharmaceutical composition as claimed in claim 7, wherein said pharmaceutical composition is made health food or nutrient.

13. a pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis, it comprises:

The ginsenoside, it comprises Rg1 and Rb1; And

The Radix Glycyrrhizae acids, it is that raw material is made by being selected from a kind of of glycyrrhizic acid, enoxolone and combination thereof.

14. pharmaceutical composition as claimed in claim 13, wherein said pharmaceutical composition comprise the described ginsenoside Rg1+Rb1 of 2～25 weight portions and the described Radix Glycyrrhizae acids of 3～46 weight portions.

15. pharmaceutical composition as claimed in claim 14, wherein said pharmaceutical composition also comprise the described ginsenoside Rg1+Rb1 of 4～12 weight portions and the described Radix Glycyrrhizae acids of 5～15 weight portions.

16. pharmaceutical composition as claimed in claim 13, wherein said pharmaceutical composition comprise that described ginsenoside is the Radix Ginseng extract that contains ginsenoside Rg1 and Rb1, and described Radix Glycyrrhizae acids is the Radix Glycyrrhizae extract that contains glycyrrhizic acid.

17. pharmaceutical composition as claimed in claim 13, wherein said pharmaceutical composition contain pharmaceutically acceptable carrier, additive or its combination.

18. pharmaceutical composition as claimed in claim 13, wherein said pharmaceutical composition is made a dosage form, described dosage form be selected from lozenge, capsule, powder, tablet, powder, solution, microcapsule, suspensoid, Emulsion, granule, drop pill, pill and the pharmaceutics oral Pharmaceutical dosage forms one of them.

19. pharmaceutical composition as claimed in claim 13, wherein said pharmaceutical composition is made health food or nutrient.

20. a pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis, it comprises:

The ginsenoside, it comprises Rg1 and Rb1;

The Radix Glycyrrhizae acids, it is selected from a kind of of glycyrrhizic acid, enoxolone and combination thereof; And

Fructus Jujubae cyclic adenosine monophosphate is that raw material is made.

21. pharmaceutical composition as claimed in claim 20, wherein said pharmaceutical composition comprise the described ginsenoside Rg1+Rb1 of 2～25 weight portions, the described Radix Glycyrrhizae acids of 3～46 weight portions and the described Fructus Jujubae cyclic adenosine monophosphate of 0.002～0.4 weight portion.

22. pharmaceutical composition as claimed in claim 21, wherein said pharmaceutical composition comprise the described ginsenoside Rg1+Rb1 of 4～12 weight portions, the described Radix Glycyrrhizae acids of 5～15 weight portions and the described Fructus Jujubae cyclic adenosine monophosphate of 0.01～0.08 weight portion.

23. pharmaceutical composition as claimed in claim 20, wherein said pharmaceutical composition comprises that described ginsenoside is the Radix Ginseng extract that contains ginsenoside Rg1 and Rb1, described Radix Glycyrrhizae acids is the Radix Glycyrrhizae extract that contains glycyrrhizic acid, and described Fructus Jujubae cyclic adenosine monophosphate is the Fructus Jujubae extract that contains Fructus Jujubae cyclic adenosine monophosphate.

24. pharmaceutical composition as claimed in claim 20, the raw material of wherein said Fructus Jujubae cyclic adenosine monophosphate is the second following extract: extract Fructus Jujubae earlier and obtain first extract, described first extract of repurity gets described second extract, and the Fructus Jujubae cyclic adenosine monophosphate concentration of wherein said second extract is higher than the Fructus Jujubae cyclic adenosine monophosphate concentration of described first extract.

25. pharmaceutical composition as claimed in claim 20, wherein said pharmaceutical composition contain pharmaceutically acceptable carrier, additive or its combination.

26. pharmaceutical composition as claimed in claim 20, wherein said pharmaceutical composition is made a dosage form, described dosage form be selected from lozenge, capsule, powder, tablet, powder, solution, microcapsule, suspensoid, Emulsion, granule, drop pill, pill and the pharmaceutics oral Pharmaceutical dosage forms one of them.

27. pharmaceutical composition as claimed in claim 20, wherein said pharmaceutical composition is made health food or nutrient.

28. the preparation method of the raw material that contains Fructus Jujubae cyclic adenosine monophosphate of a pharmaceutical composition that is used for the treatment of melancholia and anxiety neurosis, it comprises the following steps:

(a) extract Fructus Jujubae and obtain first extract; And

(b) described first extract of purification obtains second extract,

29. preparation method as claimed in claim 28, wherein step (b) is selected the Fructus Jujubae cyclic adenosine monophosphate in described first extract of macroporous resin upper prop adsorbing separation that contains aldehyde radical for use.

30. preparation method as claimed in claim 29, wherein step (b) is selected the Fructus Jujubae cyclic adenosine monophosphate in described first extract of macroporous resin OU-2 upper prop adsorbing separation that contains aldehyde radical for use.

31. preparation method as claimed in claim 30, wherein step (b) is separated Fructus Jujubae cyclic adenosine monophosphate in described first extract with macroporous resin ME-2 upper prop again.