CN100478000C - Application of valeriana wallichii and its extract in preparation of medicine for treating anxiety neurosis - Google Patents
Application of valeriana wallichii and its extract in preparation of medicine for treating anxiety neurosis Download PDFInfo
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- CN100478000C CN100478000C CNB2005100216628A CN200510021662A CN100478000C CN 100478000 C CN100478000 C CN 100478000C CN B2005100216628 A CNB2005100216628 A CN B2005100216628A CN 200510021662 A CN200510021662 A CN 200510021662A CN 100478000 C CN100478000 C CN 100478000C
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- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides the use of Valeriana jatamansi Jones and its extract in preparing medicaments for treating dysphoria. The invention also discloses a medicinal composition containing Valeriana jatamansi Jones and its extract as the active components, as well as pharmaceutically acceptable medicinal auxiliary materials.
Description
Technical field
The present invention relates to a kind of new purposes of medicine, specifically, is Rhizoma valerianae latifoliae and extract thereof the purposes in the medicine of preparation treatment anxiety neurosis, belongs to drug world.
Background technology
Anxiety neurosis be with extensive and lasting anxiety or repeatedly the outbreak terrified uneasiness be the neurosis psychosexual disorder of principal character.Its anxiety or fear often do not have flesh and blood or are not inconsistent with real situation, often with dizzy, uncomfortable in chest, cardiopalmus, rapid breathing, xerostomia, urine urgency-frequency, vegetative nerve symptom and nervousness in sports such as perspire, tremble.Primary disease comprises generalized anxiety disorder and panic disorder.Clinical in generalized anxiety disorder, 16-40 year age bracket, the women sees more.Investigation shows that China's generalized anxiety disorder sickness rate is 2%-4.7%, and the panic disorder lifetime prevalence is 1.5%-3.5%; Sickness rate can be up to more than 10% for some specific crowd (as patients with coronary heart disease, student before the examination), and the U.S. once investigated and finds have 24.5% people to live through anxiety disorder in certain lifelong period.
Anxiety Western medicine at present both at home and abroad commonly used such as tricyclic antidepressant, reversible and irreversibility oxidase inhibitor, efficient benzodiazepine, selectivity serotonin reuptake blocker etc. are because of its addiction, dependency and gastrointestinal tract, the dirty side reaction of Liver and kidney have limited their use.And the Traditional Chinese medicine for tranquilization treatment that can be used for anxiety neurosis at present all lacks specific aim and curative effect is all imprecise.
Rhizoma valerianae latifoliae is dry rhizome and the root of Valerianaceae plant valeriana Rhizoma valerianae latifoliae (Valeriana jatamansi Jones), is one of China's Chinese medicine.Put down in writing in the Compendium of Material Medica: " Rhizoma valerianae latifoliae goes out in the another name for Sichuan Province Xi Mao pine fence mountain.Grass roots also, black has thick palpus, shape such as Aranea and Rhizoma Ligustici, Rhizoma Chuanxiong, fragrant odour ".1977 the version Chinese Pharmacopoeia (one one) once recorded, describing its function is regulating QI to relieve pain, antiinflammatory antidiarrheal, expelling wind and removing dampness, is used for wrist abdominal distention and pain, dyspepsia, diarrhoea, dysentery, rheumatic arthralgia and soreness of the waist and knees etc.Pharmacological research shows that Rhizoma valerianae latifoliae has the various biological activity.Have antibiotic and viral, the effect of bringing high blood pressure down as its extract, and can significantly prolong the barbital sodium mouse sleep time, increase sleeping number of mice, reduce the effect of mouse writhing reaction times, illustrate that it has calm and certain analgesic activities.Rhizoma valerianae latifoliae iridoid constituents also has cell toxicant and antitumor action.But the effect that do not appear in the newspapers Rhizoma valerianae latifoliae or its iridoid constituents have the anxiety neurosis of preventing and treating.
Summary of the invention
Technical scheme of the present invention has provided a kind of new purposes of medical material, further, is Rhizoma valerianae latifoliae and extract thereof the purposes in the medicine of preparation treatment anxiety neurosis.Another technical scheme of the present invention has provided that to contain by Rhizoma valerianae latifoliae medical material or Rhizoma valerianae latifoliae ethanol extraction or Rhizoma valerianae latifoliae iridoid constituents be pharmaceutical composition of active component and preparation method thereof.
Rhizoma valerianae latifoliae and extract thereof the purposes in the medicine of preparation treatment anxiety neurosis.
Wherein, described Rhizoma valerianae latifoliae derives from dry rhizome and the root of Herba Patriniae section plant Rhizoma valerianae latifoliae (Valeriana jatamansi Jones).
Further, described Rhizoma valerianae latifoliae extract is Aranea perfume or extractive with organic solvent.
Wherein, described Rhizoma valerianae latifoliae extract is the Rhizoma valerianae latifoliae ethanol extraction.
Contain Rhizoma valerianae latifoliae iridoid constituents in the described Rhizoma valerianae latifoliae ethanol extraction, wherein, the weight percentage that the iridoid composition accounts for total extract is: 30-80%.
The present invention also provides the purposes of Rhizoma valerianae latifoliae iridoid constituents in the medicine of preparation treatment anxiety neurosis.
The invention provides a kind of pharmaceutical composition for the treatment of anxiety neurosis, it is to contain by the former green powder of Rhizoma valerianae latifoliae or Rhizoma valerianae latifoliae ethanol extraction or Rhizoma valerianae latifoliae iridoid constituents to be active component, to add the oral formulations that acceptable accessories or complementary composition are prepared from.
Wherein, described oral formulations is tablet, capsule, granule or oral liquid.
The invention provides a kind of method for preparing the pharmaceutical composition for the treatment of anxiety neurosis, it is characterized in that: it comprises the steps:
A, get the Rhizoma valerianae latifoliae medical material and directly beat powder; Or the Rhizoma valerianae latifoliae powder added the 60%-95% alcohol reflux get ethanol extraction, Rhizoma valerianae latifoliae extract; Or the 60%-95% alcohol reflux is got ethanol extraction obtain Rhizoma valerianae latifoliae iridoid constituents by macroporous adsorbent resin;
B, with Rhizoma valerianae latifoliae powder, ethanol extraction or Rhizoma valerianae latifoliae iridoid constituents, add acceptable accessories or complementary composition and be prepared into preparation pharmaceutically commonly used.
Wherein, the Rhizoma valerianae latifoliae iridoid constituents described in the step a, its preparation method is: get the Rhizoma valerianae latifoliae pulverizing medicinal materials, 90% alcohol reflux, extracting solution concentrate and add water, fling to ethanol, with 70% alcohol flushing of macroporous resin on the concentrated solution, collect eluent, promptly.
The present invention provides a kind of new selection for the clinical treatment anxiety neurosis, and this medicine is treated anxiety neurosis, determined curative effect, no addiction and dependency, no obvious toxic and side effects targetedly.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
The specific embodiment
The preparation of embodiment 1 Rhizoma valerianae latifoliae iridoid constituents of the present invention
Get Rhizoma valerianae latifoliae medical material 200g and smash to pieces, add 90% alcohol reflux 2 times, each 6 times of amounts, merge extractive liquid, is evaporated to small size.Add suitable quantity of water, fling to ethanol in the water-bath, get macroporous resin on the concentrated solution, and use 70% alcohol flushing, collect eluent and also reclaim solvent promptly.
The preparation of embodiment 2 Rhizoma valerianae latifoliae iridoid constituents of the present invention
Get Rhizoma valerianae latifoliae medical material 200g and smash to pieces, add 60% alcohol reflux 2 times, each 6 times of amounts, merge extractive liquid, is evaporated to small size.Add suitable quantity of water, fling to ethanol in the water-bath, get macroporous resin on the concentrated solution, and use 70% alcohol flushing, collect eluent and also reclaim solvent promptly.
The preparation of embodiment 3 Rhizoma valerianae latifoliae iridoid constituents of the present invention
Get Rhizoma valerianae latifoliae medical material 200g and smash to pieces, add 95% alcohol reflux 2 times, each 6 times of amounts, merge extractive liquid, is evaporated to small size.Add suitable quantity of water, fling to ethanol in the water-bath, get macroporous resin on the concentrated solution, and use 70% alcohol flushing, collect eluent and also reclaim solvent promptly.
The preparation of embodiment 4 Rhizoma valerianae latifoliae extracts of the present invention
Get Rhizoma valerianae latifoliae medical material 200g and smash to pieces, add the analytical pure methanol eddy and extract 2 times, each 5 times of amounts, merge extractive liquid,, concentrating under reduced pressure, concentrated solution carries out silica gel column chromatography, and with petrol ether/ethyl acetate (volume ratio 15: 1), collects eluent and reclaim solvent promptly.
The preparation of embodiment 5 Rhizoma valerianae latifoliae ethanol extractions of the present invention
Get Rhizoma valerianae latifoliae medical material 200g and smash to pieces, add 90% alcohol reflux 2 times, each 6 times of amounts, merge extractive liquid, reclaims solvent promptly.
The preparation of embodiment 6 medicines of the present invention
Get the Rhizoma valerianae latifoliae iridoid constituents of embodiment 1 preparation, add appropriate amount of starch as adjuvant, tabletting promptly gets tablet of the present invention.
The preparation of embodiment 7 medicines of the present invention
Get the Rhizoma valerianae latifoliae ethanol extraction of embodiment 2 preparations, granulate, drying adds an amount of Pulvis Talci, and mix homogeneously incapsulates and makes capsule.
The preparation of embodiment 8 medicines of the present invention
Get Rhizoma valerianae latifoliae medical material 200g and pulverize, add 90% alcohol reflux 2 times, each 6 times of amounts, merge extractive liquid, reclaims solvent, is drying to obtain the extractum powder.Semen Ziziphi Spinosae 200g pulverizes, and adds 1200ml, 1000ml respectively, the 800ml decocting boils three times, and each 1 hour, three times decocting liquid filtered, and mixes, and spray drying gets the extractum powder.Rhizoma valerianae latifoliae dry extract and Semen Ziziphi Spinosae dry extract mix, and add an amount of Pulvis Talci, and mix homogeneously incapsulates and makes capsule.
The assay of embodiment 9 Rhizoma valerianae latifoliae iridoid constituents
Extract 0.45um filtering with microporous membrane with embodiment 1～5 preparation, using HPLC detects Rhizoma valerianae latifoliae iridoid constituents valepotriate, acetyl valepotriate and dihydro valepotriate, mobile phase is second eyeball-water (volume ratio 50: 60), detection wavelength valepotriate 256nm, acetyl valepotriate are 256nm, and the dihydro valepotriate is 210nm.The result: with valepotriate, acetyl valepotriate, the dihydro valepotriate is an index components, and the weight percentage that the iridoid composition accounts for total extract is: 30-80%.
Below prove beneficial effect of the present invention by pharmacodynamics test.
The angst resistance effect experiment of test example 1 Rhizoma valerianae latifoliae extract
1 materials and methods
1.1 material
1.1.1 laboratory animal
The Kunming white mice, male, body weight 18～22g is divided into 5 groups at random, 10 every group.
1.1.2 medicine and reagent
Stable: with the required concentration solution of normal saline furnishing.
Rhizoma valerianae latifoliae iridoids component extract: press the preparation of embodiment 1 method, with the required concentration solution of normal saline furnishing.
1.1.3 instrument and equipment
Wooden overhead cross is lost, the light and shade case.
1.2 experimental technique
1.2.1 mice elevated plus-maze test
Wooden overhead cross is lost by two open access (30cm * 5cm) and two closed access (30cm * 5cm * 15cm) forms, its cross part (the title central authorities of 5cm * 5cm) chamber of setting out.
Give the Rhizoma valerianae latifoliae iridoids component extract gastric infusion of the high, medium and low dosage of mice (0.6g/kg, 0.3g/kg, 0.15g/kg), continuous 7 days.Mice placed overhead cross labyrinth central area in 1 hour after the administration in the 7th day, every mice 5min that once experimentizes; Stable matched group is stabilized (1mg/kg) and is experimentized simultaneously after 1 hour.In the record 5min animal enter out arm and the number of times that closes arm and opening arm with close in the arm and the labyrinth central area in movement time and move distance.With enter out arm number of times and the percentage of always going into the arm number of times when in opening arm movement time with open the percentage ratio that arm closes the total time in the arm and represent the angst resistance effect index.
1.2.2 mice light and shade case experiment
The length and width height of mice light and shade case is respectively 44cm * 21cm * 21cm, is divided into camera-lucida and camera bellows, and camera-lucida accounts for 2/3, and camera bellows accounts for 1/3, has a duck eye freely to pass through for mice between the light and shade case.There is the incandescent lamp bulb of 100W the camera-lucida top, and the illumination at the bottom of the camera-lucida case is 100Lux.Tested afternoon and carry out.The same elevated plus-maze test of administrated method, after the medication, mice placed the movable 20min of prologue after, write down mice in the 10min with register and between camera-lucida and camera bellows, wear the case number of times.
1.2.3 date processing
After data carry out variance analysis with each group, adopt the t check, adopt the SPSS10.0 statistical software to calculate.
2, result
2.1 the mice elevated plus-maze test the results are shown in Table 1
Table 1 enters out the arm number of times and always goes into the arm number of times, opens the percentage ratio (X ± S) of movement time in the arm and total time in arm
※ shows with the normal control group and compares: p＜0.05, ※ ※ compares with the normal control group: p＜0.01, ※ ※ ※ compares with the normal control group: p＜0.001.
The result shows, Rhizoma valerianae latifoliae iridoids component extract can increase the movement time of animal in opening arm and the percentage ratio of always going into the arm time, do not increase and always go into arm number of times (always going into the locomotor activity that the arm number of times is represented animal), illustrate that medicine of the present invention has angst resistance effect (p＜0.05 or p＜0.01 or p＜0.001) on this model.
2.2 mice light and shade case experimental result sees Table 2
Table 2 mice light and shade case is worn case number of times (X ± S)
※ shows with the normal control group and compares p＜0.05
The result shows, antianxiety drugs is stabilized what 1mg/kg can increase animal and worn the case number of times, has angst resistance effect.What Rhizoma valerianae latifoliae iridoids component extract can increase animal wears case number of times (p＜0.05), has angst resistance effect on this model.
3, discuss
Overhead cross labyrinth and light and shade case are classical anxiety models.On the model of overhead cross labyrinth, animal is reflected the anxiety of animal to the habit of probing into of novel environment with the contradiction state that the fear of uphanging out arm is formed animal.Mice light and shade case is to utilize the dark light anxiety model that the characteristics of probing into set up of becoming reconciled of disliking of mice happiness.These two models all are the habits of probing into of utilizing animal, because of the simple to operate and convenient and swift research that is widely used in antianxiety drug.On the model of the overhead cross of mice labyrinth, Rhizoma valerianae latifoliae iridoids component extract can significantly increase the percentage rate of the movement time of mice in opening arm; And can significantly increase mice and between the light and shade case, wear the case number of times, on these two models, all demonstrate clear and definite angst resistance effect.
The studies on acute toxicity of test example 2 Rhizoma valerianae latifoliae iridoids component extracts
1, materials and methods
1.1 animal and medicine
Animal: 20 of Kunming kind white mice, male and female half and half, age in 6-8 week, body weight 18-22g, Sichuan Province's laboratory animal Professional Committee plant provides.The quality certification number: real moving Guan Zhidi 2004-15 number of river.
Medicine: Rhizoma valerianae latifoliae iridoids component extract, the viscosity that is formulated as medicinal liquid can be by irritating stomach syringe needle Cmax.
1.2 experimental technique
Mice adapts to a week at Animal House, tests last curfew food and can't help water 12 hours.
Next day, accurately each mice body weight of weighing is irritated gastric capacity 0.4ml/10g with the mice maximum, and branch is irritated stomach 2 times and is subjected to the reagent thing in 1 day, observes continuously 7 days.
1.3 observation index
Comprise the weight of animals variation, diet, outward appearance, behavior, secretions, Excreta, poisoning and death condition etc.All animals carry out gross anatomy after the observation period finishes, when any organ volume, color, quality etc. occur and changes, should write down and carry out histopathological examination.
2, result
The same day after the mice medication, free movable obviously minimizing, mental status peace and quiet, appetite has minimizing in various degree, and 2-3 days, it is normal that the activity of animal, appetite etc. are recovered all gradually.Observed 7 days continuously, animal all survives, and tangible poisoning symptom and death condition do not occur, activity freely, hair smoothing, diet is normal, defecation is normal, weight increase, no abnormal secretions such as nose, eye, oral cavity.Finish experiment and dissect mice, the naked eyes and the microscopic examination important organ heart, liver, spleen, lung, kidney, gastrointestinal etc. are not all found obvious pathological changes.
3, conclusion
From this experiment as can be known, only calculate by being subjected to reagent 16% concentration and mice one day to irritate gastric capacity 1.6ml/20g/, the filling stomach dosage of every mice is 12.8g/kg, 640 times of usual amounts every day (0.02g/kg) that is equivalent to be grown up, show that drug toxicity of the present invention is very little, clinical practice is safe and reliable.
Above-mentioned pharmacodynamics, toxicology test prove that medicine of the present invention is treated anxiety neurosis, determined curative effect, no addiction and dependency targetedly, and no obvious toxic and side effects provides a kind of new selection for clinical.
Claims (1)
1, the purposes of Herba Patriniae section plant Rhizoma valerianae latifoliae Valeriana jatamansi Jones iridoid constituents in the medicine of preparation treatment anxiety neurosis.
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| CN101164554B (en) * | 2006-08-11 | 2011-08-10 | 通威股份有限公司 | Application of valeriana jatamansi jones in preparing veterinary medicine for treating pica |
| CN103145724A (en) * | 2013-03-12 | 2013-06-12 | 西南交通大学 | Novel iridoids compound and neuroprotective effect thereof |
| CN104800201B (en) * | 2014-01-28 | 2017-09-29 | 北京中医药大学 | A kind of purposes of compound |
| EP3367831A4 (en) * | 2015-10-30 | 2019-08-14 | Nisarga Biotech Private Limited | Therapeutic compositions comprising herbal extracts and essential oils for smoking and vaporization |
| CN110368378A (en) * | 2018-04-11 | 2019-10-25 | 西南交通大学 | Jatamans valeriana rhizome element E is preparing the purposes in mGluR2 and mGluR3 receptor stimulant medicine |
| CN109293621A (en) * | 2018-11-21 | 2019-02-01 | 兰州大学 | A single compound of spider incense extract and its application in the drug for the treatment of Alzheimer's disease |
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