CN102153608A - Method for preparing raw material containing Chinese date cyclic adenosine monophosphate of medicinal composition with multi-target receptor afteraction mechanism for treating melancholia - Google Patents
Method for preparing raw material containing Chinese date cyclic adenosine monophosphate of medicinal composition with multi-target receptor afteraction mechanism for treating melancholia Download PDFInfo
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Abstract
The invention discloses a method for preparing a raw material containing Chinese date cyclic adenosine monophosphate of a medicinal composition with a multi-target receptor afteraction mechanism for treating melancholia, which comprises the following steps of: (a) carrying out extraction on Chinese dates to obtain first extract; and (b) purifying the first extract to obtain second extract, wherein the concentration of Chinese date cyclic adenosine monophosphate of the second extract is higher than the concentration of Chinese date cyclic adenosine monophosphate of the first extract. An experiment proves that by adopting the medicinal composition prepared according to the preparation method, the rat tail suspension immobility time can be obviously shortened and the time for body temperature dropping by induction of reserpine can be obviously reduced. An experiment result proves that compared with a mainstream medicament (Paroxetine) for treating melancholia in the prior art, the medicinal composition prepared according to the preparation method has obvious effect of resisting melancholy.
Description
The application is to be on November 30th, 2007 applying date, and application number is 200710194686.2, and denomination of invention is divided an application for the application of " mechanism of action is used for the treatment of hypochondriacal pharmaceutical composition behind the multi-target receptor ".
Technical field
The present invention relates to one group to comprise ginsenoside Rg1, Rb1 and Potenlini and date cyclic monophosphate (date cyclic adenosine monophosphate, date cAMP) raw material, make the preparation method that mechanism of action behind the multi-target receptor is used for the treatment of the raw material that contains the date cyclic monophosphate of hypochondriacal pharmaceutical composition, the preparation method who relate in particular to that a kind of effective component is clear and definite, curative effect is taken the raw material that contains the date cyclic monophosphate of safe, as to avoid causing side effects such as strong vomiting hypochondriacal oral pharmaceutical of treatment or protective foods obviously, for a long time.
Background technology
Melancholia is a kind of common disease, and nearly 25% women lives through melancholia in life at it in general population according to statistics, has about 10% to live through melancholia (Zhang Chunxing work: " pop psychology ") among the male sex approximately.The data that The World Health Organization (WHO) provides: melancholia is about 11% at global sickness rate, the whole world has 3.4 hundred million depressed patients approximately at present, and this numeral still becomes ascendant trend, and investigation finds that melancholia will rise to world's second largest common disease at 20 years from now on.
In the prior art, Remeron is based on Prozac, seroxat, Zoloft etc. (5-HT, NE, the DA reuptake inhibitors of classes such as SSRI, SNRI, NDRI), 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 of having asked the city all has side effect in various degree, for example: increase homicide rate, headache, dizziness, dizzy, insomnia, drowsiness, tinnitus, dry, apocleisis, appetite increases, body weight rising, increased blood pressure, gastrointestinal upset, gastric disorder causing nausea, nauseating, vomiting, maldigestion, diarrhoea, constipation, melosalgia, skin eruption, tremble, spasm, hidrosis, oedema, sexual desire reduction, sexual dysfunction etc.Remeron such as Prozac 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 children and teenager commit suiside.Wherein, seroxat just was found as far back as 1996 especially and has potential safety hazard, began to recall from the market successively from calendar year 2001.In June, 2004, the New York, United States chief procurator accuses Britain GlaxoSmithKline PLC company in order to obtain profit, and duplicity has concealed takes related research report between seroxat and " increasing the risk of teenager's introgression and behavior ".Under this background, how to research and develop the problem that the low medicine that obviously anti-melancholy effect can be arranged again of side effect of new generation has become global the world of medicine and paid close attention to.
In recent years, the scientists of international the world of medicine new breakthrough occurring aspect the research of melancholia pathogenesis, discovery is except the re-uptake suppressor mode treatment melancholia with 5-HT, NE, DA, more can take to regulate behind the acceptor mode of mechanism of action and treat melancholia, and owing to mechanism of action behind the acceptor is regulated the class medicine and enumerated the research and development focus that the appearance of pula (Rolipram) becomes the world of medicine's Remeron.Enumerating the pula is that (phosphodiesterase 4 for four type phosphodiesterases, PDE4) inhibitor, clinical trial shows that it has significantly anti-melancholy effect, but enumerate the pula and strong vomiting can occur owing to take, so be forced to stop research and development, yet enumerate the research and development thinking that a new generation's " mechanism of action antidepressant drug behind the acceptor " has but been opened up in the pula.
In sum, the applicant is after having understood the limitation that is had in the known technology, through concentrated research and discovery, and in line with the spirit of working with perseverance, finally having found " mechanism of action is used for the treatment of the pharmaceutical composition of dysthymia disorders behind the multi-target receptor " of the present invention, 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, Potenlini and date cAMP, make mechanism of action behind the multi-target receptor and be used for the treatment of that the oral pharmaceutical or the protective foods, particularly effective component of dysthymia disorders is clear and definite, curative effect is taken safe, as can not cause side effects such as strong vomiting new solution obviously, for a long time.
The solution of medicine of the present invention is the result who concentrates on studies and explore through the contriver, treat hypochondriacal pathology and pharmacology theory according to modern medicine, particularly mechanism of action antidepressant target research behind the bind receptor, prove through a large amount of experimentation on animalies: ginsenoside contains adenylate cyclase (adenylate cyclase, AC) stimulate adenosine, and contain the inhibition composition of cAMP phosphodiesterase (CAPD); Potenlini (glycyrrhetinic acid) is cAMP phosphodiesterase (CAPD) potent inhibitor.Ginsenoside, the two compatibility of Potenlini (glycyrrhetinic acid), synergy, can further improve availability and the activity of cAMP, 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 glucocorticosteroid hpa axis), thus reach significant anti-melancholy function.In addition, date cAMP can also improve the expression of human body cAMP, thereby play anti-melancholy effect, the date cAMP of content in the date atomic (about ten thousand/) is extracted and purified into the Fructus Jujubae extract that contains 1% date cAMP resists the zooperal result of tentative depressed effect to show, has significantly anti-tentative depressed function, but only heat extraction and be not further purified the Fructus Jujubae extract that improves its extract date cAMP concentration by for example water of routine, but do not have significantly anti-tentative depressed function though contain the date cAMP of trace, in order further to strengthen anti-melancholy effect of the present invention, also can be with date cAMP, ginsenoside and Potenlini three compatibility.Genseng, Radix Glycyrrhizae, date have been the traditional Chinese medical science and tonic herbal cuisine medicinal material and food commonly used since several thousand, in edible and clinical use in 1,100, fully prove the security of genseng, Radix Glycyrrhizae, date three compatibility, contriver research and result of experiment prove these three kinds of medicinal materials if only the decoction method that uses with routine extracts the extract of gained and is used for the treatment of hypochondriacal Remeron at present and compares not possess and resist melancholy curative effect significantly; But the purifying mode of taking for example to go up column chromatography again further improves the concentration of effective ingredients such as ginsenoside Rg1 contained in the extract, Rb1 and date cAMP, add raw materials such as Potenlini or glycyrrhetinic acid and make and be used for the treatment of hypochondriacal medicine, through the animal experiment proof be used for the treatment of hypochondriacal Remeron at present and compare to have and resist melancholy function significantly; Collect three kinds of medicinal material extract and go up column chromatography purification and obtain remaining residue behind the extract, though detect ginsenoside Rg1, Rb1, Potenlini and the date cAMP that the back contains trace with high performance liquid phase, through the not significant anti-melancholy function of proof behind the animal experiment; And take genseng, side effects such as strong vomiting can not take place in Radix Glycyrrhizae and date, so the contriver proposes with the ginsenoside Rg1, Rb1 and Potenlini and date cAMP are raw material, mechanism of action is used for the treatment of hypochondriacal oral pharmaceutical or protective foods after making multi-target receptor, particularly except for example water, outside the ethanol equal solvent is heated and is extracted further purifying improve ginsenoside Rg1 in the extract, it is clear and definite that the raw material of Rb1 and date cAMP concentration adds that raw materials such as containing Potenlini or glycyrrhetinic acid is made effective component, curative effect is obvious, take safe for a long time, the new solution that can not cause side effects such as strong vomiting is to improve the weak point that is had in the known technology.
Pharmaceutical composition of the present invention compares with the medicine target of enumerating the anti-melancholy in pula and mechanism of action
The Remeron of mechanism of action is enumerated the pula difference behind medicine of the present invention and the known acceptor, be both can be same pass through that mechanism of action reaches anti-melancholy effect behind the multi-target receptor, can avoid again as taking side effects such as enumerating behind the pula caused strong vomiting.
Because being converted into the transformation efficiency of glycyrrhetinic acid in human body, Potenlini almost reaches 100%, and the fat-soluble glycyrrhetinic acid stronger than Potenlini can enter in the brain through hemato encephalic barrier, so playing anti-melancholy effect, Potenlini inhibition CAPD undertaken by being converted into glycyrrhetinic acid in the body, therefore, can be that raw material is processed into pharmaceutical composition of the present invention with Potenlini or glycyrrhetinic acid.
The present invention has disclosed the pharmaceutical composition that mechanism of action behind a kind of multi-target receptor is used for the treatment of dysthymia disorders, and described pharmaceutical composition is made by the raw material that comprises ginsenoside Rg1, Rb1 and Potenlini or glycyrrhetinic acid.
Preferably, pharmaceutical composition of the present invention is by comprising that ginsenoside (Rg1+Rb1) adds up to the raw material of 2～26 weight parts and Potenlini or glycyrrhetinic acid 3～48 weight parts made.
Preferably, pharmaceutical composition of the present invention is by comprising that ginsenoside (Rg1+Rb1) adds up to the raw material of 4～13 weight parts and Potenlini or glycyrrhetinic acid 5～16 weight parts made.
According to another notion of the present invention, the present invention has disclosed the pharmaceutical composition that mechanism of action behind a kind of multi-target receptor is used for the treatment of dysthymia disorders, and described pharmaceutical composition is made by the raw material that comprises ginsenoside Rg1, Rb1 and Potenlini or glycyrrhetinic acid and date cAMP.
Preferably, pharmaceutical composition of the present invention is by comprising that ginsenoside (Rg1+Rb1) adds up to the raw material of 2～26 weight parts and Potenlini or glycyrrhetinic acid 3～48 weight parts and date cAMP 0.002～0.5 weight part made.
Preferably, pharmaceutical composition of the present invention is by comprising that ginsenoside (Rg1+Rb1) adds up to the raw material of 4～13 weight parts and Potenlini or glycyrrhetinic acid 5～16 weight parts and date cAMP 0.01～0.1 weight part made.
Preferably, pharmaceutical composition of the present invention can comprise pharmaceutically acceptable carrier or additive, can make known oral Pharmaceutical dosage forms on any pharmaceuticies such as lozenge, capsule, powder, tablet, pulvis, solution, microcapsule, suspensoid, emulsion, granule, pill, pill.
Preferably, described pharmaceutical composition can be used to make medicine, protective foods and the nutrition agent that is used for the treatment of dysthymia disorders.
The present invention has also disclosed the preparation method that mechanism of action behind a kind of multi-target receptor is used for the treatment of the raw material that contains the date cyclic monophosphate of hypochondriacal pharmaceutical composition, and it comprises the following steps:
(a) extract date and obtain first extract; And
(b) described first extract of purifying obtains second extract,
The date cyclic monophosphate concentration of wherein said second extract is higher than the date cyclic monophosphate concentration of described first extract.
Preferably, wherein step (b) can be selected date cyclic monophosphate in described first extract of macroporous resin upper prop fractionation by adsorption that contains aldehyde radical for use.
Preferably, wherein step (b) can be selected date cyclic monophosphate in described first extract of macroporous resin OU-2 upper prop fractionation by adsorption that contains aldehyde radical for use.
Preferably, wherein step (b) can be again separated date cyclic monophosphate in described first extract with macroporous resin ME-2 upper prop.
Be used for the treatment of hypochondriacal oral pharmaceutical described in specification sheets 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 traditional 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 polygala root glucoside, saikoside, glycycoumarin etc.) in identical other of efficacy effect.The adding of this routine simplifies cuts out and starts the Chinese medicine of agent or effective constituent substitutes accordingly with other similar or identical CAPD inhibitor of effect mechanism, AC; all belong to art technology and researchist's general technical activity, so it is all within protection scope of the present invention.
Can understand the present invention better by consulting accompanying drawing and describing in detail.
Summary of drawings
Fig. 1 is the method flow synoptic diagram of the preparation embodiment of the invention 1 medicine.
Fig. 2 is the method flow synoptic diagram of the preparation embodiment of the invention 2 medicines.
Fig. 3 is the method flow synoptic diagram of the preparation embodiment of the invention 3 medicines.
Fig. 4 is the method flow synoptic diagram of the preparation embodiment of the invention 4 medicines.
Fig. 5 is the method flow synoptic diagram of the preparation embodiment of the invention 5 medicines.
Fig. 6 is the method flow synoptic diagram of the preparation embodiment of the invention 6 medicines.
Better embodiment of the present invention
Further specify the present invention below with reference to drawings and Examples.The present invention adopts to well known to a person skilled in the art that method prepares 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 that mechanism of action behind a kind of multi-target receptor is used for the treatment of dysthymia disorders, and described pharmaceutical composition is made by the raw material that comprises ginsenoside Rg1, Rb1 and Potenlini or glycyrrhetinic acid.
Scheme one:
To contain the raw material of ginsenoside Rg1, Rb1 and Potenlini or glycyrrhetinic acid, be processed into multi-target receptor of the present invention after mechanism of action be used for the treatment of hypochondriacal pharmaceutical composition.
Scheme two:
To contain the raw material that ginsenoside (Rg1+Rb1) adds up to 2～26 weight parts and Potenlini or glycyrrhetinic acid 3～48 weight parts, be processed into pharmaceutical composition of the present invention.
Scheme three:
To contain the raw material that ginsenoside (Rg1+Rb1) adds up to 4～13 weight parts and Potenlini or glycyrrhetinic acid 5～16 weight parts, be processed into pharmaceutical composition of the present invention.
Scheme four:
To contain raw materials such as ginsenoside Rg1, Rb1, Potenlini or glycyrrhetinic acid and date cAMP, be processed into multi-target receptor of the present invention after mechanism of action be used for the treatment of hypochondriacal pharmaceutical composition.
Scheme five:
To contain the raw material that ginsenoside (Rg1+Rb1) adds up to 2～26 weight parts, Potenlini or glycyrrhetinic acid 3～48 weight parts and date cAMP 0.002～0.5 weight part, be processed into pharmaceutical composition of the present invention.
Scheme six:
To contain the raw material that ginsenoside (Rg1+Rb1) adds up to 4～13 weight parts, Potenlini or glycyrrhetinic acid 5～16 weight parts and date cAMP 0.01～0.1 weight part, be processed into pharmaceutical composition of the present invention.
Scheme seven:
Pharmaceutical composition of the present invention can comprise pharmaceutically acceptable carrier or additive, can make known oral Pharmaceutical dosage forms on any pharmaceuticies such as lozenge, capsule, powder, tablet, pulvis, solution, microcapsule, suspensoid, emulsion, granule, pill, pill.
Scheme eight:
Pharmaceutical composition of the present invention can be used to make medicine, protective foods and the nutrition agent that is used for the treatment of dysthymia disorders.
In order to finish purpose of the present invention, the special making method that proposes following medicine.
Method one:
Extracting the extract that contains ginsenoside Rg1, Rb1 and Potenlini in genseng and Radix Glycyrrhizae is raw material, or the direct raw material that contains ginsenoside Rg1, Rb1 and Potenlini or glycyrrhetinic acid that has been prepared into of employing, be processed into multi-target receptor of the present invention after mechanism of action be used for the treatment of hypochondriacal pharmaceutical composition.
Method two:
To contain the raw material that ginsenoside (Rg1+Rb1) adds up to 2～26 weight parts and Potenlini or glycyrrhetinic acid 3～48 weight parts, be processed into pharmaceutical composition of the present invention.
Method three:
To contain the raw material that ginsenoside (Rg1+Rb1) adds up to 4～13 weight parts and Potenlini or glycyrrhetinic acid 5～16 weight parts, be processed into pharmaceutical composition of the present invention.
Method four:
Extracting the extract that contains ginsenoside Rg1, Rb1, Potenlini and date cAMP in genseng and Radix Glycyrrhizae and date is raw material, or the direct raw material that contains ginsenoside Rg1, Rb1, Potenlini or glycyrrhetinic acid and date cAMP that has been prepared into of employing, be processed into multi-target receptor of the present invention after mechanism of action be used for the treatment of hypochondriacal pharmaceutical composition.
Method five:
To contain the raw material that ginsenoside (Rg1+Rb1) adds up to 2～26 weight parts, Potenlini or glycyrrhetinic acid 3～48 weight parts and date cAMP 0.002～0.5 weight part, be processed into pharmaceutical composition of the present invention.
Method six:
To contain the raw material that ginsenoside (Rg1+Rb1) adds up to 4～13 weight parts, Potenlini or glycyrrhetinic acid 5～16 weight parts and date cAMP 0.01～0.1 weight part, be processed into pharmaceutical composition of the present invention.
Method seven:
Pharmaceutical composition of the present invention can comprise pharmaceutically acceptable carrier or additive, can make known oral Pharmaceutical dosage forms on any pharmaceuticies such as lozenge, capsule, powder, tablet, pulvis, solution, microcapsule, suspensoid, emulsion, granule, pill, pill.
Method eight:
With the method for raw material of the present invention, be processed into the present invention and be used for the treatment of hypochondriacal protective foods according to protective foods manufacturing standard.
Specific embodiment
Further specify the present invention below with reference to the drawings and specific embodiments.
Embodiment 1
See also Fig. 1, it is the method flow synoptic diagram of the preparation embodiment of the invention 1 medicine.In Fig. 1, earlier with after the genseng fragmentation of 20kg with the extraction of heating of 70% ethanolic soln, through last column chromatographic isolation and purification, drying, must contain the Radix Ginseng extract 0.8kg of 120g ginsenoside (Rg1+Rb1); Then, again with soak at room temperature after the Radix Glycyrrhizae fragmentation of 10kg 12 hours, with water extraction and alcohol precipitation method extract, concentrate drying, must contain the Radix Glycyrrhizae extract 2kg of Potenlini 200g; Afterwards, after Radix Ginseng extract 150g that aforesaid method is obtained and Radix Glycyrrhizae extract 200g pulverize and mix, 350g (containing 22.5g ginsenoside Rg1+Rb1 and 20g Potenlini) the present invention program's one pharmaceutical composition.
Embodiment 2
See also Fig. 2, it is the method flow synoptic diagram of the preparation embodiment of the invention 2 medicines.In Fig. 2, be prepared into purity be the Radix Ginseng extract 200g of 96% glycyrrhetinic acid 3.96g and embodiment 1 gained pulverize mix after, 203.96g (containing 30g ginsenoside Rg1+Rb1 and 3.8g glycyrrhetinic acid) the present invention program's two pharmaceutical composition.
Embodiment 3
See also Fig. 3, it is the method flow synoptic diagram of the preparation embodiment of the invention 3 medicines.In Fig. 3, with the 3.4g purity that has been prepared into be 90% ginsenoside Rg1,7.8g purity be 90% ginsenoside Rb1 and 36.8g purity be 95% Potenlini pulverize mix after, 48g (containing 10g ginsenoside Rg1+Rb1 and 35g Potenlini) the present invention program's three pharmaceutical composition.
Embodiment 4
See also Fig. 4, it is the method flow synoptic diagram of the preparation embodiment of the invention 4 medicines.In Fig. 4, add the water soak at room temperature after the date fragmentation with 10kg, extract with water extraction and alcohol precipitation method again and obtain the date extracting solution, use macroporous resin OU-2, the successively continuous upper prop fractionation by adsorption of ME-2 two posts, drying again, the Fructus Jujubae extract 30g that must contain date 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 and mix, 353g (containing 22.5g ginsenoside Rg1+Rb1,20g Potenlini and 0.03g date cAMP) the present invention program's four pharmaceutical composition.
Embodiment 5
See also Fig. 5, it is the method flow synoptic diagram 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 and mixes, 350.5g (containing 22.5g ginsenoside Rg1+Rb1,20g Potenlini and 0.005g date cAMP) the present invention program's five pharmaceutical composition.
Embodiment 6
See also Fig. 6, it is the method flow synoptic diagram of the preparation embodiment of the invention 6 medicines.In Fig. 6, with the 6.8g purity that has been prepared into be 90% ginsenoside Rg1,15.6g purity be 90% ginsenoside Rb1,26g purity be Fructus Jujubae extract 10g that 96% glycyrrhetinic acid and embodiment 4 obtain pulverize mix after, 58.4g (containing 20g ginsenoside Rg1+Rb1,25g glycyrrhetinic acid and 0.1g date cAMP) the present invention program's six pharmaceutical composition.
The influence of 1 pair of mouse tail suspension experiment of experimental example one embodiment
1.1 laboratory animal
The ICR mouse, 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 laboratory apparatus: stopwatch.
1.4 dosage design
Embodiment 1 high dosage: 80mg/kg/d, middle dosage: 40mg/kg/d and low dosage: 20mg/kg/d.
1.5 experimental technique and result
1.5.1 grouping administration
With the mouse random packet, 10 every group: 1. embodiment 1 high dose group (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 1; 3. embodiment 1 low dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. physiological 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 goes out on the batten of table top 5cm to suspend in midair 6 minutes, write down the dead time of mouse in back 5 minutes.
1.5.3 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
1.5。4 experimental results
Experimental result sees also table 1.
The influence of table 1,1 pair of mouse dead time of embodiment
Annotate: compare * P＜0.05**P＜0.01 with model group
Conclusion:
According to above experiment, the embodiment of the invention 1 height, 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 physiological 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 mouse reserpine induction of experimental example 2 embodiment body temperature descends
2.1 laboratory animal
The ICR mouse, 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.
2.2 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.
Serpentine: Guangdong Bangmin Pharmaceutical Co., Ltd..
2.3 laboratory apparatus
GM222 type electronic thermometer, stopwatch.
2.4 dosage design
Embodiment 1 high dosage: 80mg/kg/d, middle dosage: 40mg/kg/d and low dosage: 20mg/kg/d.
2.5 experimental technique and result
2.5.1 grouping administration
With the mouse random packet, 10 every group: 1. embodiment 1 high dose group (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 1; 3. embodiment 1 low dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. physiological saline group (PO).
2.5.2 experimental technique
After administration in the 8th day, measured mouse anus temperature in 1 hour,, behind the injection serpentine, measured mouse anus temperature in 4 hours more then through abdominal injection serpentine 2mg/kg.The degree of depth and time homogeneous that each thermometric chronothermometer inserts the mouse anus cause.
2.5.3 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
2.5.4 experimental result
Experimental result sees also table 2.
The influence that table 2,1 pair of mouse reserpine induction of embodiment body temperature descend
Annotate: compare * P＜0.05**P＜0.01 with model group
Conclusion:
According to above experiment, the embodiment of the invention 1 high, medium and low 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.
The influence of 2 pairs of mouse tail suspension experiments of experimental example 3 embodiment
3.1 laboratory animal
The ICR mouse, 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.
3.2 experimental drug
Embodiment 2: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.
Paroxetine (seroxat): Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.
3.3 laboratory apparatus
Stopwatch.
3.4 dosage design
Embodiment 2 high dosages: 80mg/kg/d, middle dosage: 40mg/kg/d and low dosage: 20mg/kg/d.
3.5 experimental technique and result
3.5.1 grouping administration
With the mouse random packet, 10 every group: 1. embodiment 2 high dose group (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 2; 3. embodiment 2 low dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. physiological saline group (PO).Hang tail in 1 hour after the last administration tests.
3.5.2 experimental technique
Mouse tail (apart from tail point 1cm place) is bonded at head height with adhesive plaster goes out on the batten of table top 5cm to suspend in midair 6 minutes, write down the dead time of mouse in back 5 minutes.
3.5.3 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
3.5.4 experimental result
Experimental result sees also table 3.
The influence of table 3,2 pairs of mouse dead times of embodiment
Annotate: compare * P＜0.05**P＜0.01 with model group
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 physiological 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 mouse reserpine inductions of experimental example 4 embodiment body temperature descends
4.1 laboratory animal
The ICR mouse, 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.
4.2 experimental drug
Embodiment 2: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.
Paroxetine (seroxat): Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.
Serpentine: Guangdong Bangmin Pharmaceutical Co., Ltd..
4.3 laboratory apparatus
GM222 type electronic thermometer, stopwatch.
4.4 dosage design
Embodiment 2 high dosages: 80mg/kg/d, middle dosage: 40mg/kg/d and low dosage: 20mg/kg/d.
4.5 experimental technique and result
4.5.1 grouping administration
With the mouse random packet, 10 every group: 1. embodiment 2 high dose group (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 2; 3. embodiment 2 low dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. physiological saline group (PO).
4.5.2 experimental technique
After administration in the 8th day, measured mouse anus temperature in 1 hour,, behind the injection serpentine, measured mouse anus temperature in 4 hours more then through abdominal injection serpentine 2mg/kg.The degree of depth and time homogeneous that each thermometric chronothermometer inserts the mouse anus cause.
4.5.3 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
4.5.4 experimental result
Experimental result sees also table 4.
The influence that table 4,2 pairs of mouse reserpine inductions of embodiment body temperature descend
Annotate: compare * P＜0.05**P＜0.01 with model group
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 5 embodiment
5.1 laboratory animal
The ICR mouse, 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.
5.2 experimental drug
Embodiment 3: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.
Paroxetine (seroxat): Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.
5.3 laboratory apparatus:
Stopwatch.
5.4 dosage design
Embodiment 3 high dosages: 80mg/kg/d, middle dosage: 40mg/kg/d and low dosage: 20mg/kg/d.
5.5 experimental technique and result
5.5.1 grouping administration
With the mouse random packet, 10 every group: 1. embodiment 3 high dose group (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 3; 3. embodiment 3 low dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. physiological saline group (PO).Hang tail in 1 hour after the last administration tests.
5.5.2 experimental technique
Mouse tail (apart from tail point 1cm place) is bonded at head height with adhesive plaster goes out on the batten of table top 5cm to suspend in midair 6 minutes, write down the dead time of mouse in back 5 minutes.
5.5.3 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
5.5.4 experimental result
Experimental result sees also table 5.
The influence of table 5,3 pairs of mouse dead times of embodiment
Annotate: compare * P＜0.05**P＜0.01 with model group
Conclusion:
According to above experiment, the embodiment of the invention 3 height, 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 physiological 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 mouse reserpine inductions of experimental example 6 embodiment body temperature descends
6.1 laboratory animal
The ICR mouse, 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.
6.2 experimental drug
Embodiment 3: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.
Paroxetine (seroxat): Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.
Serpentine: Guangdong Bangmin Pharmaceutical Co., Ltd..
6.3 laboratory apparatus
GM222 type electronic thermometer, stopwatch.
6.4 dosage design
Embodiment 3 high dosages: 80mg/kg/d, middle dosage: 40mg/kg/d and low dosage: 20mg/kg/d.
6.5 experimental technique and result
6.5.1 grouping administration
With the mouse random packet, 10 every group: 1. embodiment 3 high dose group (80mg/kg, PO, administration 7d); 2. dosage group (40mg/kg, PO, administration 7d) among the embodiment 3; 3. embodiment 3 low dose group (20mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. physiological saline group (PO).
6.5.2 experimental technique
After administration in the 8th day, measured mouse anus temperature in 1 hour,, behind the injection serpentine, measured mouse anus temperature in 4 hours more then through abdominal injection serpentine 2mg/kg.The degree of depth and time homogeneous that each thermometric chronothermometer inserts the mouse anus cause.
6.5.3 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
6.5.4 experimental result
Experimental result sees also table 6.
The influence that table 6,3 pairs of mouse reserpine inductions of embodiment body temperature descend
Annotate: compare * P＜0.05**P＜0.01 with model group
Conclusion:
According to above experiment, the embodiment of the invention 3 high, medium and low 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 7 embodiment experiment
7.1 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. (conformity certification numbering SCXK (capital) 2002-0003).
7.2 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% cellulose sodium carboxymethyl (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 serotonin (5-HT) standard substance are Sigma company product; Other reagent is commercially available.
7.3 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.
7.4 experimental technique
7.4.1 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% cellulose sodium carboxymethyl (CMC-Na) by reagent and positive drug.Gastric infusion once a day.
7.4.2 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 encephalic 2 seconds with special electric iron, destroy olfactory bulb, with styptic sponge used filling bone window skin suture; (intraperitoneal IP) gives and benzylpenicillin sodium 40,000 units/Kg per 4 days of postoperative, and gives continuously and be subjected to the reagent thing 24 days with abdominal injection.
7.5 observation index
7.5.1 open wild experiment
Open wild experimental box and be configured to by light blue glued board 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).
7.5.2 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 latent period) first, and this is a school grade.Repeated test 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.
7.6 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
7.7 experimental result
See also table 7 7.7.1 open wild experimental result.
Table 7, olfactory bulb are damaged rat model and are opened wild experimental result
Annotate: compare * P＜0.05**P＜0.01 with model group
See also table 8 7.7.2 keep away dark experimental result.
Table 8, olfactory bulb are damaged rat model and are kept away dark experimental result
Annotate: compare * P＜0.05**P＜0.01 with model group
Conclusion:
Experimental example 7 results show: embodiment 4 high dose group can obviously be improved olfactory bulb and damage the rat level and the vertical movement that are caused and increase, the vertical movement increase that the dosage group is damaged rat model to olfactory bulb among the embodiment 4 effect that also has clear improvement.In addition, the effect of also having clear improvement that embodiment 4 height, the middle dosage group rat that damage is caused to olfactory bulb are learnt and memory function goes down.
The unpredictable influence that stress test for a long time of 4 pairs of rats of experimental example 8 embodiment
8.1 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. (conformity 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% cellulose sodium carboxymethyl (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 serotonin (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% cellulose sodium carboxymethyl (CMC-Na) by reagent and positive drug.Gastric infusion once a day.
8.4.2 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 mouse box), 3 illuminations all night, 34 ℃ of cold water swimming 5 minutes, 3 45 ℃ of baking boxs heat baking 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.
8.5 observation index
8.5.1 open wild experiment: the same.
8.5.2 passive avoidance experiment: the same.
8.5.3 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.
8.5.4 body weight test
The increased value of body weight before and after relatively each treated animal is tested.
8.5.5 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 tap water.Weighing record rat is drunk the heavy difference of bottle of 1 hour front and back of sucrose water and calculates each sucrose water amount of drinking.The difference of syrup intake during relatively each group is tested each time.
8.5.6 high performance liquid phase-electrochemical detection method
Measure NE and 5-HT content in the rat cerebral cortex.
8.6 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
8.7 experimental result
8.7.1 rat drink sucrose water yield result sees also table 9.
Table 9, the long-term Stress model rat drink of the unpredictability sucrose water yield
Annotate: compare * P＜0.05**P＜0.01 with model group
8.7.2 the rat body weight incremental result sees also table 10.
Table 10, the long-term Stress model rat body weight of unpredictability increment
Annotate: compare * * P＜0.01 with model group
8.7.3 rat forced swimming experiment dead time result sees also table 11.
Table 11, the long-term Stress model rat of unpredictability forced swimming experiment dead time
Annotate: compare * P＜0.05, * * P＜0.01 with model group
8.7.4 rat opens wild experimental result and sees also table 12.
Table 12, the long-term Stress model rat of unpredictability open wild experimental result
Annotate: compare * P＜0.05, * * P＜0.01 with model group
8.7.5 rat is kept away dark experimental result and sees also table 13.
Table 13, the long-term Stress model rat of unpredictability are kept away dark experimental result
Annotate: compare * P＜0.05**P＜0.01 with model group
8.7.6 NE and 5-HT content detection result see also table 14 in the rat cerebral cortex.
NE and 5-HT content in table 14, the long-term Stress model rat cerebral cortex of unpredictability
Annotate: compare * P＜0.05**P＜0.01 with model group
Conclusion:
Experimental example 8 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 senior middle school's low dose group all can obviously increase the rat forced swimming experiment dead time; Embodiment 4 high dose group can obviously be improved rat level and the vertical movement minimizing that the long-term stress stimulation of unpredictability is caused, and embodiment 4 low dose group reduce the effect that also has clear improvement to the rat vertical movement that the long-term stress stimulation of unpredictability is caused; The rat learning capacity that embodiment 4 low dose group are caused the long-term stress stimulation of unpredictability reduces the improvement effect; Embodiment 4 senior middle school's low dose group all can obviously increase NE and 5-HT content in the rat cerebral cortex.
The influence of 5 pairs of mouse tail suspension experiments of experimental example 9 embodiment
9.1 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 physiological saline preparation back Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.
9.2 animal
The ICR mouse, male, body weight 20.0 ± 1g, secondary is provided by the department of the Chinese Academy of Sciences of Department Of Medicine, Peking University laboratory animal section, animal quality conformity certification SCXK (capital) 2006-0008.
9.3 instrument
Stopwatch.
9.4 method
70 of mouse are divided into 5 groups at random, dosage group (40mg/kg/d), embodiment 5 low dose group (20mg/kg/d) among NS group, paroxetine group (3mg/kg/d), embodiment 5 high dose group (80mg/kg/d), the embodiment 5.Every day gastric infusion once, mouse 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 mouse be the state of hanging by the feet, the mouse head is about 10cm apart from the bottom surface, suspended in midair 6 minutes, and write down the accumulation dead time of mouse in back 5 minutes.
9.5 statistical procedures
Experimental data with
Expression, experimental result is carried out one-way analysis of variance with SPSS 11.5 statistical softwares.
9.6 result
Mouse tail suspension experiment dead time result sees also table 15.
The influence of table 15,5 pairs of mouse tail suspension experiment accumulation dead times of embodiment
Annotate: compare * P＜0.05**P＜0.01 with the NS group
Conclusion:
Result of study shows that embodiment 5 high, medium and low three dosage groups and clinical effective thymoleptic 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 mouse forced swimming experiments of experimental example 10 embodiment
10.1 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 physiological saline preparation back Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.
10.2 animal
The ICR mouse, male, body weight 20.0 ± 1g, secondary is provided by the department of the Chinese Academy of Sciences of Department Of Medicine, Peking University laboratory animal section, animal quality conformity certification SCXK (capital) 2006-0008.
10.3 instrument
Stopwatch.
10.4 method
Mice group and administration are tested as mouse tail suspension.Experiment is respectively organized mouse and is experimentized after 1 hour in administration, reach mouse training swimming in the 8th day 15 minutes before testing, test after 24 hours, mouse 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 mouse in water.
10.5 statistical procedures
Experimental data with
Expression, experimental result is carried out one-way analysis of variance with SPSS 11.5 statistical softwares.
10.6 result
Mouse forced swimming experimental result sees also table 16.
The influence of table 16,5 pairs of mouse forced swimming experiments of embodiment
Annotate: compare * P＜0.05**P＜0.01 with the NS group
Conclusion:
Result of study shows that embodiment 5 high, medium and low dosage groups and clinical effective thymoleptic paroxetine all can obviously shorten the mouse forced swimming accumulation dead time, shows that embodiment 5 has the depressed effect of certain anti-experimental character.
Experimental example 11
0.9 kilogram of 7 kilograms of last 9 kilograms of genseng residues, Radix Glycyrrhizae residues and date residue will be collected after embodiment 1 and embodiment 4 extractions, must contain ginsenoside Rg1, Rb1, and the residue mixture of Potenlini and date cAMP of denier after being dried, pulverizing, mixing, carry out controlled trial the influence of mouse tail suspension experiment.
11.1 laboratory animal
The ICR mouse, 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.
11.2 experimental drug
Residue mixture: Beijing Ounaer B iological Engineering and Technology Co., Ltd. provides.
Paroxetine (seroxat): Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product.
11.3 laboratory apparatus
Stopwatch.
11.4 dosage design
Residue mixture high dosage: 160mg/kg/d, middle dosage: 80mg/kg/d reach, low dosage: 40mg/kg/d.
11.5 experimental technique and result
11.5.1 grouping administration
With the mouse random packet, 10 every group: 1. residue mixture high dose group (160mg/kg, PO, administration 7d); 2. dosage group (80mg/kg, PO, administration 7d) in the residue mixture; 3. residue mixture low dose group (40mg/kg, PO, administration 7d); 4. paroxetine group (3mg/kg, PO, administration 7d); 5. physiological saline group (PO).Hang tail in 1 hour after the last administration tests.
11.5.2 experimental technique
Mouse tail (apart from tail point 1cm place) is bonded at head height with adhesive plaster goes out on the batten of table top 5cm to suspend in midair 6 minutes, write down the dead time of mouse in back 5 minutes.
11.5.3 statistical procedures
Experimental data is used
Expression, experimental result is carried out variance analysis with SPSS 11.5 statistical softwares.
11.5.4 experimental result
Experimental result sees also table 17.
Table 17, residue mixture are to the influence of mouse dead time
Annotate: compare * P＜0.05**P＜0.01 with model group
Conclusion:
According to above experiment, though high, medium and low 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 this residue mixture does not have the depressed function of anti-experimental character with physiological saline group (model group).
The present invention is used for the treatment of the range of application of the oral drugs of melancholia:
1. in the oral drugs that are used for the treatment of melancholia of the present invention, can contain acceptable additive on the materia medica;
The oral drugs that are used for the treatment of melancholia of the present invention it can be processed into powder, capsule agent, tablet, etc. various known formulations; And
3. the oral drugs that are used for the treatment of melancholia of the present invention can be made the health food that is used for the treatment of melancholia.
Those skilled in the art can make various improvement to the present invention, and do not break away from the protection domain such as claims.
Claims (4)
1. mechanism of action is used for the treatment of the preparation method of the raw material that contains the date cyclic monophosphate of hypochondriacal pharmaceutical composition behind the multi-target receptor, and it comprises the following steps:
(a) extract date and obtain first extract; And
(b) described first extract of purifying obtains second extract,
The date cyclic monophosphate concentration of wherein said second extract is higher than the date cyclic monophosphate concentration of described first extract.
2. preparation method as claimed in claim 1, wherein step (b) is selected the date cyclic monophosphate in described first extract of macroporous resin upper prop fractionation by adsorption that contains aldehyde radical for use.
3. preparation method as claimed in claim 2, wherein step (b) is selected the date cyclic monophosphate in described first extract of macroporous resin OU-2 upper prop fractionation by adsorption that contains aldehyde radical for use.
4. preparation method as claimed in claim 3, wherein step (b) is separated date cyclic monophosphate in described first extract with macroporous resin ME-2 upper prop again.
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| WO2021052153A1 (en) * | 2019-09-17 | 2021-03-25 | 中国药科大学 | Application of cyclic adenosine monophosphate, derivatives thereof or prodrugs thereof in preparation of drugs for preventing and/or treating depressive disorder |
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| WO2021052153A1 (en) * | 2019-09-17 | 2021-03-25 | 中国药科大学 | Application of cyclic adenosine monophosphate, derivatives thereof or prodrugs thereof in preparation of drugs for preventing and/or treating depressive disorder |
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Application publication date: 20110817 |