CN105582068A - Application of cooked rhubarb micro-powder in preparation of anti-anxiety drug - Google Patents
Application of cooked rhubarb micro-powder in preparation of anti-anxiety drug Download PDFInfo
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- CN105582068A CN105582068A CN201511005895.9A CN201511005895A CN105582068A CN 105582068 A CN105582068 A CN 105582068A CN 201511005895 A CN201511005895 A CN 201511005895A CN 105582068 A CN105582068 A CN 105582068A
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- rhizoma rhei
- prepared radix
- micro mist
- anxiety
- micro
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/708—Rheum (rhubarb)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/17—Preparation or pretreatment of starting material involving drying, e.g. sun-drying or wilting
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Abstract
The invention discloses an application of cooked rhubarb micro-powder in preparation of an anti-anxiety drug and further provides pharmaceutical composition. The pharmaceutical composition is a traditional Chinese medicine preparation prepared from the cooked rhubarb micro-powder as an active ingredient and pharmaceutically acceptable auxiliary materials or adjuvant components. The cooked rhubarb micro-powder treats anxiety disorder in a targeted manner, has definite curative effect, does not cause addiction or dependence and does not have obvious toxic or side effects.
Description
Technical field
Application one technical field of prepared RADIX ET RHIZOMA RHEI micro mist in preparation treatment anxiety disorder product the invention belongs to Chinese medicine neckTerritory, relates generally to the new medicine use of the main processed product prepared RADIX ET RHIZOMA RHEI of Chinese herb rhubarb and preparation thereof, is specifically related to itThe application in preparation treatment anxiety disorder product.
Background technology
Anxiety disorder (anxietydisoders) anxiety neurosis that is otherwise known as is a kind of taking anxiety as mainNeurosis. Clinically taking anxiety as cardinal symptom, main clinical manifestation is without clear and definite objective objectsNervous worry, be on tenterhooks and vegetative nerve functional disturbance symptom (palpitaition, perspiration, hand are trembled, frequent micturition etc.),To cause the particularly Important cause of disease of neuropsychiatric disease of many chronic diseases. Generally we divide itBecome generalized anxiety disorder and these two kinds of forms of panic disorder.
Along with the increase of life stress, its incidence of disease raises year by year, and public health problem has become international.Also become the 2nd large burden disease and the incidence of disease rises year by year in China's anxiety disorder. At present treatment taking doctor trained in Western medicine asMain, Benzodiazepines, tricyclic antidepressants anxiolytic, selective five hydroxytryptamine reuptaking inhibitor, 5-hydroxyl for multiselectTryptamines and norepinephrine dual reuptake inhibitor etc., but above-mentioned a few class medicine is equal in application processHave side effect in various degree, as dizziness headache, n and V, dry, constipation, even Pi Shen, flesh pine,The serious adverse reactions such as maincenter calmness, habituation or abstinence syndrome. And in therapeutic process for the state of an illnessHeavier patient is for ensureing malignant boil effect more options large dose oral administration or selecting medicine Synergistic treatment of more than two kinds, longPhase is taken easy generation drug resistance and habituation in a large number, and drug withdrawal is easily recurred. In recent years, Chinese medicine anxiety disorderResearch report increase gradually, it is evident in efficacy, has obviously reduced side effects of pharmaceutical drugs.
The main aspect that Chinese medicine is different from natural drug is exactly to use after " processing is concocted ", and the traditional Chinese medical science existsWhen using drugs to form a prescription, be particular about very much again " life of medicine is ripe ", " raw ripe different use ". The raw ripe medicine materical crude slice of Chinese medicine not only in the property of medicine andIn profile, there is variation, and variation is also occurring aspect chemical composition and pharmacological action. Prepared RADIX ET RHIZOMA RHEI is doneFor an important processed product of rheum officinale, be not only subject to doctor and be widely used, and in document to its processing action alsoThere is certain discussion. Sun Simiao points out rheum officinale suitable " the raw use of real person, empty person's wine steams " in " silver-colored Nereid is micro-". BrightLuo Zhouyan, Zhang Jiebin etc. also think and use after valetudinarian, invalid answers wine to cook again. " danxi's experiential therapy " said, rheum officinale " raw usingLogical stomach is stopped up heat, and ripe use is separated all sore purge the sthenic heart-fires ". Dou Hanqing thinks with the method for " nine soak nine steaming nine solarizations "The prepared RADIX ET RHIZOMA RHEI of concocting has effect of " having benefit in rushing down ". As can be seen here, rheum officinale has the characteristic of raw ripe different use,Doctor admits this viewpoint mostly at all times. In fact comprehensive, prepared RADIX ET RHIZOMA RHEI is concocted object roughly two, one, relaxes and rushes downThe side effect of the lower and gas that injures one's stomach, impairment of yin blood, the 2nd, change property of medicine trend, strengthen or outstanding clearing heat and detoxicating, liveBlood stagnation resolvation effect. Have no report prepared RADIX ET RHIZOMA RHEI and anthraquinone component thereof and talan methods of glycosides and there is antianxietyEffect.
Summary of the invention
The object of this invention is to provide the purposes of prepared RADIX ET RHIZOMA RHEI micro mist in preparation anxiety disorder medicine, micro-with prepared RADIX ET RHIZOMA RHEIPowder is active component manufacture control and prevention of anxiety disease drug, and described anxiety disorder comprises the Secondary cases that anxiety causesLearning and memory decline or/and Anhedonia.
Described prepared RADIX ET RHIZOMA RHEI micro mist derives from the dry root of polygonaceae plant Rheum officinale RheumofficinaleBaill.Stem; Concocting method is: 1) rhubarb scrapes off crust, cuts sheet or piece, makes at 30 DEG C of-50 DEG C of low temperature dryingsRhubarb tablets or piece, 2) concoct: mix the yellow rice wine 30kg of 15-16% for every 100kg rhubarb tablets or piece with yellow rice wine thoroughly;Within vexed 1.5 hours, be sucked to wine, put in high-pressure sterilizing pot and steam 6 hours, take out, dry; 3) prepared RADIX ET RHIZOMA RHEIThe preparation of micro mist: get process of preparing Chinese medicine gained prepared RADIX ET RHIZOMA RHEI medicinal material and throw in micronizer, pulverize 5-8min, to obtain final product,Particle diameter is: 50-78 μ m.
It is little that zoopery shows that the prepared RADIX ET RHIZOMA RHEI micro mist through as above concocting has toxicity, to the study of anxiety disorder secondaryDecrease of memory etc. have obvious mitigation. Prepared RADIX ET RHIZOMA RHEI micro mist or using it as active component composition medicinalCompositions etc. comprise endogenous anxiety disorder, reactive anxiety disorder, invisible anxiety for the preparation of prevention or treatmentDisease, drug-induced Secondary cases anxiety, climacteric or postpartum anxiety, brain trauma or the cerebral apoplexy anxiety of bringing outAnd anxiety neurosis merges anxiety in the application of the medicine of interior various anxiety symptoms with for diabetesDisease, and decline for the preparation of the insecondary learning and memory preventing and treatment anxiety disorder causes, anhedoniaEtc. the application in the medicine of symptom.
Another technical scheme of the present invention provides a kind of pharmaceutical composition for the treatment of anxiety disorder, micro-with prepared RADIX ET RHIZOMA RHEIPowder is active component, adds the extract oral agent that pharmaceutically acceptable auxiliary material or adjuvanticity composition are prepared fromPreparation.
Further analyze and show that prepared RADIX ET RHIZOMA RHEI micro mist contains active principle Anthraquinones and talan glycoside activityComposition.
The pharmaceutical composition of the treatment anxiety disorder the invention provides, containing prepared RADIX ET RHIZOMA RHEI micro mist is active component,Add the Chinese medicine preparation that pharmaceutically acceptable auxiliary material or complementary composition are prepared from.
Wherein said Chinese medicine preparation is tablet, capsule, granule or oral liquid.
Detailed description of the invention
Zoopery is below to further description of the present invention, but and does not mean that of the present inventionAny restriction.
Animal used as test: male Kunming is SPF level mouse, body weight 30 ± 2g; Male SPF level SD rat,Male, body weight 215 ± 5g, is purchased from Chengdu and reaches rich fruit and test Company of Animals Ltd., SCXK[river] 2008-24. OftenIt accepts 12h illumination/12h dark, and periodicity of illumination is 8:00-20:00, and 20 ± 2 DEG C of laboratory temperatures are wetDegree 60%, animal can absorb standard feed and cleaning water voluntarily, and International Laboratory Animal is observed in zooperyEthics requirement.
Medicine:
Rhubarb medicinal material, purchased from new lotus rheum officinale planting base, Chengdu, Sichuan, is concocted teaching and research through Chengdu University of Traditional Chinese MedicineThe first penetrating judgment of chamber Lu is awarded the dry rhizome that is accredited as polygonaceae plant Rheum officinale RheumofficinaleBaill..Concocting method is, rhubarb: scrape off crust, cut sheet or piece, low temperature (30 DEG C-50 DEG C) is dried; RipeRheum officinale: get rhubarb sheet or piece appropriate, mix thoroughly with yellow rice wine, put wine in vexed 1.5 hours and be sucked, set high to press and go outIn bacterium pot, steam 6 hours, take out, dry. Every 100kg rhubarb tablets or piece, use yellow rice wine 30kg (wine degree:15-16％)。
The preparation of prepared RADIX ET RHIZOMA RHEI micro mist: get process of preparing Chinese medicine gained prepared RADIX ET RHIZOMA RHEI medicinal material and throw in micronizer, pulverize 5-8min,Obtain. Particle diameter is: 50-78 μ m.
Surazepam (estazolam sheet): Pharmaceutical Co Ltd, Changzhou Pharmaceutical Factory No.4
0.9% physiological saline: Kelun Pharm Ind Co., Ltd., Sichuan
Experimental program:
1, elevated plus-maze test
The passage of an opening more can evoke the avoiding reaction of animal with respect to the passage of a sealing, andThe behavior such as rat can produce some strange fears, approach-avoidance conflict with it, probe into. Elevated plus-maze test isUtilize rodent to the curiosity of novel environment and the psychology that the fear of uphanging unlimited arm is formed to contradiction,Thereby simulation anxiety disorder. Concrete modeling method be calculate rat enter out the arm time of staying (openarmtime,OT) with the percentage of opening arm number of times (openarmentry, OE) and account for respectively total time and total degree, reflection animalAnxiety state, using this as anxiety evaluate index. The method quilt in anxiety disorder drug screening is wide at presentGeneral application.
1.1 mouse experiment
The overhead cross of PM-200 mouse labyrinth is cross, and wherein one group of relative edge's both sides has a baffle plate,Be called the closure arm in overhead cross labyrinth; Other one group of relative edge's both sides do not have baffle plate, are open arms. ?Overhead cross labyrinth is put into rather dark place, with the trickle work can distinguish mouse apart from 1.5m placeMove as the best, keep laboratory perseverance bright. Install the video camera in overhead cross labyrinth. Open PM-200 tenWord labyrinth video tracking analysis software, the position of adjusting video camera, the lower overhead cross fan of the function that makes to make a video recording recordThe whole track in palace
Experimental technique
100 random packet of KM male mice be Normal group, prepared RADIX ET RHIZOMA RHEI micro mist suspension high, in,Low dose group, positive drug group, amounts to 5 groups, every group of 20 animals, each treated animal dosage regimen is as follows:
(1) Normal group: the oral distilled water of giving;
(2) prepared RADIX ET RHIZOMA RHEI micro mist suspension high dose group 5g/kg.d;
(3) dosage group 2.5g/kg.d in prepared RADIX ET RHIZOMA RHEI micro mist suspension;
(4) prepared RADIX ET RHIZOMA RHEI micro mist suspension low dose group 1.25g/kg.d
(5) stable group 1mg/kg.d
Be administered once every day, 14d continuously, and blank group gives distilled water, last administration or distilled water 30minAfter, mouse is put into elevated plus-maze test device, observe the behavior performance in mouse 5min, and useSoftware is recorded related data.
The impact of table 1 prepared RADIX ET RHIZOMA RHEI mouse OE% and OT% (n＝20)
Note: with blank group Bi ， ﹡ ﹡ P < 0.01, compare ﹡ P < 0.05; With relatively #P < 0.05 of stable group, ##P < 0.01 (lower same).
Table 2 prepared RADIX ET RHIZOMA RHEI on mouse probe number of times and enter arm total degree impact (n＝20)
Table 3 prepared RADIX ET RHIZOMA RHEI on mouse stand number of times and enter central area number of times impact (n＝20)
From table 1 to table 3, compared with blank group, high, medium and low three the dosage group mouse of prepared RADIX ET RHIZOMA RHEIOE% and OT% significantly increase (P < 0.01), and probe number of times significantly increases (P < 0.01), enters arm total degreeIncrease (P < 0.05), the number of times of standing significantly reduces (P < 0.01), and entering central number of times increases (P < 0.05);Compared with stable group, in prepared RADIX ET RHIZOMA RHEI, dosage group mouse OE% and OT% significantly increase (P < 0.01), ripe largeYellow high dose group and the middle dosage group number of times of standing reduces (P < 0.05), and prepared RADIX ET RHIZOMA RHEI high dose group probe number of times increasesAdd (P < 0.05), the low dense dosage group of prepared RADIX ET RHIZOMA RHEI is entered arm total degree increases (P < 0.05).
From the above experimental results, medicine of the present invention has angst resistance effect on this model.
1.2 rat experiment
The overhead cross of PM-200 rat labyrinth: the overhead cross of rat labyrinth is cross, and there is one of baffle plate both sidesGroup relative edge is the closure arm in the overhead cross of rat labyrinth; And relative edge's both sides do not have one group of opposite side of baffle plateIt is the overhead cross of rat labyrinth open arms. Overhead cross labyrinth is put into the more dim place of light, withBeyond the distance of 1m, can distinguish the trickle activity of rat for best. Install and adjust overhead cross labyrinthCamera. Open the video tracking analysis software in the overhead cross of rat labyrinth, the position of adjusting camera,Make camera just can record the whole track the best in overhead cross labyrinth, adjust each ginseng of softwareNumber preparing experiment.
Experimental technique
SD rat adaptability is fed one week, is divided at random 4 groups after weighing, 10 every group; Be respectively: justNormal group, normal administration group, model group and model administration group. Model group and model administration group are carried out 4 cyclesChronic unpredictable sexual stimulus (CUMS) set up depression and anxiety disorder model, proceed to the 4th weekPhase starts administration. Each treated animal dosage regimen is as follows:
(1) Normal group: the oral distilled water of giving;
(2) normal administration group 2.5g/kg.d;
(3) the oral distilled water of giving of model group;
(4) model administration group 2.5g/kg.d
Last administration or give after physiological saline 30min the experiment of rat being put into the overhead cross of PM-200 labyrinthIn device, observe the behavior performance in rat 5min, and software gets off relevant data record by experimentFor subsequent use.
The overhead cross of table 4 labyrinth rat behavior learn OE% and OT% impact (n＝10)
Note: with normal group Bi ， ﹡ ﹡ P < 0.01, compare ﹡ P < 0.05; With relatively #P < 0.05 of model group, ##P < 0.01 (lower same)
The overhead cross of table 5 labyrinth rat behavior learn probe number of times and enter arm total degree (n＝10)
The overhead cross of table 6 labyrinth rat stand number of times and enter central area number of times (n＝10)
From table 4, to table 6, with Normal group comparison, model group rat enters out the percentage of arm number of timesThan obviously reducing (P < 0.01); With model group comparison, it is obvious that prepared RADIX ET RHIZOMA RHEI group enters out the percentage of arm number of timesIncrease (P < 0.01); Entering arm total degree increases (P < 0.05), and the number of times there was no significant difference of standing, in enteringCentre number of times increases (P < 0.05), shows that prepared RADIX ET RHIZOMA RHEI all has angst resistance effect to intact animal and stressed animal.
From the above experimental results, medicine of the present invention has angst resistance effect on this model.
2 mouse light and shade case experiments.
The length, width and height of mouse light and shade case are respectively 44cm × 21cm × 21cm, are divided into camera-lucida and camera bellows, camera-lucidaAccount for 2/3, camera bellows accounts for 1/3. Between light and shade case, there is a duck eye can provide mouse freely to pass through. Camera-lucida topThere is the fluorescent lamp of 100w, at the bottom of camera bellows case, have electric current to pass through. The experiment of mouse light and shade case is classical Anxiety ModelExperiment. Grouping and dosage regimen are with 1.1. After medication, mouse is placed in to prologue after movable 20 minutes, with countingDevice is write down mouse in 10 minutes and wear case number of times between camera-lucida and camera bellows.
Table 7 mouse light and shade case wear case number of times (n＝20)
Note: with normal group Bi ， ﹡ ﹡ P < 0.01, compare ﹡ P < 0.05
Result shows, anxiolytic stabilize can increase animal at 1mg/kg wear case number of times, there is antianxiety and doWith. What high, the middle low dose group of prepared RADIX ET RHIZOMA RHEI can increase animal wears case number of times (P < 0.05), on this modelThere is angst resistance effect.
Claims (5)
1. the purposes of prepared RADIX ET RHIZOMA RHEI micro mist in preparation anxiety disorder medicine, taking prepared RADIX ET RHIZOMA RHEI micro mist as active component manufacture control with prevention of anxiety disease drug, described anxiety disorder comprises that the insecondary learning and memory that anxiety causes declines or/and Anhedonia.
2. purposes according to claim 1, is characterized in that, described prepared RADIX ET RHIZOMA RHEI micro mist derives from the dry rhizome of polygonaceae plant Rheum officinale RheumofficinaleBaill.; Concocting method is: 1) rhubarb scrapes off crust, cuts sheet or piece, makes rhubarb tablets or piece, 2 at 30 DEG C of-50 DEG C of low temperature dryings) concoct: mix the yellow rice wine 30kg of 15-16% for every 100kg rhubarb tablets or piece with yellow rice wine thoroughly; Within vexed 1.5 hours, be sucked to wine, put in high-pressure sterilizing pot and steam 6 hours, take out, dry; 3) preparation of prepared RADIX ET RHIZOMA RHEI micro mist: get process of preparing Chinese medicine gained prepared RADIX ET RHIZOMA RHEI medicinal material and throw in micronizer, pulverize 5-8min, to obtain final product, particle diameter is: 50-78 μ m.
3. purposes according to claim 2, is characterized in that: in described prepared RADIX ET RHIZOMA RHEI micro mist, contain Anthraquinones compound, talan glycosides compound and polysaccharide.
4. treat a pharmaceutical composition for anxiety disorder, taking prepared RADIX ET RHIZOMA RHEI micro mist as active component, add the extract oral agent formulation that pharmaceutically acceptable auxiliary material or adjuvanticity composition are prepared from.
5. pharmaceutical composition according to claim 4, is characterized in that, described oral formulations is tablet, capsule, granule or oral liquid.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201511005895.9A CN105582068A (en) | 2015-12-29 | 2015-12-29 | Application of cooked rhubarb micro-powder in preparation of anti-anxiety drug |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201511005895.9A CN105582068A (en) | 2015-12-29 | 2015-12-29 | Application of cooked rhubarb micro-powder in preparation of anti-anxiety drug |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101961326A (en) * | 2010-10-29 | 2011-02-02 | 西南交通大学 | Application of physcion in preparing medicines for treating depression |
| CN101961325A (en) * | 2010-10-29 | 2011-02-02 | 西南交通大学 | Application of emodin in preparation of drugs for treating depression |
| CN101972310A (en) * | 2010-10-14 | 2011-02-16 | 中国科学院昆明植物研究所 | Anti-anxiety medicine by using rheum officinate root extract as active ingredient, and method and application thereof |
| CN102958516A (en) * | 2009-02-20 | 2013-03-06 | N.V.努特里西阿公司 | Use of resveratrol or another hydroxylated stilbene for preserving cognitive functioning |
-
2015
- 2015-12-29 CN CN201511005895.9A patent/CN105582068A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102958516A (en) * | 2009-02-20 | 2013-03-06 | N.V.努特里西阿公司 | Use of resveratrol or another hydroxylated stilbene for preserving cognitive functioning |
| CN101972310A (en) * | 2010-10-14 | 2011-02-16 | 中国科学院昆明植物研究所 | Anti-anxiety medicine by using rheum officinate root extract as active ingredient, and method and application thereof |
| CN101961326A (en) * | 2010-10-29 | 2011-02-02 | 西南交通大学 | Application of physcion in preparing medicines for treating depression |
| CN101961325A (en) * | 2010-10-29 | 2011-02-02 | 西南交通大学 | Application of emodin in preparation of drugs for treating depression |
Non-Patent Citations (3)
| Title |
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| 孙晶单: "《中药材养生大全》", 28 February 2007, 南海出版公司 * |
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