CN105497160A - Application of prepared rhubarb micro powder in preparing medicine for treating depression - Google Patents
Application of prepared rhubarb micro powder in preparing medicine for treating depression Download PDFInfo
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- CN105497160A CN105497160A CN201511004608.2A CN201511004608A CN105497160A CN 105497160 A CN105497160 A CN 105497160A CN 201511004608 A CN201511004608 A CN 201511004608A CN 105497160 A CN105497160 A CN 105497160A
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/708—Rheum (rhubarb)
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
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Abstract
The invention discloses application of prepared rhubarb micro powder in preparing medicine for treating depression and further provides a medicine composition. The medicine composition is a traditional Chinese medicine preparation which is prepared from the prepared rhubarb micro powder serving as an active ingredient and auxiliary materials or auxiliary ingredients capable of being pharmaceutically accepted. The medicine has the application of being specifically used for the medicine for preventing and treating endogenous depression or/and reactive depression or/and masked depression or/and secondary depression caused by medicine or/and climacteric or postnatal depression or/and depression induced by cerebral trauma or strokes or/and depressive neurosis. The curative effect is definite, addiction and dependency are avoided, and no obvious toxic or side effect exists.
Description
Technical field
Application-the technical field of Radix Et Rhizoma Rhei micropowder in preparation treatment anxiety neurosis product the invention belongs to the field of Chinese medicines, relate generally to the new medicine use of the main processed product Radix Et Rhizoma Rhei of Chinese herb rhubarb and preparation thereof, be specifically related to them and preparing the application in Cure of depression product.
Background technology
Depression is the major disease that sickness rate is higher.Depression is the common disease of a kind of psychiatric department, add up according to World Health Organization (WHO), depression has become the large illness in the world the 4th, China's the 2nd large Disease Spectrum, predicts the year two thousand twenty, may become the second largest disease being only second to coronary heart disease, account for 15% of global disease burden, the sickness rate of lifelong depression is between 6%-8%, and along with the progressively aging of population, the sickness rate of depression more than 60 years old in crowd will up to 20%-50%.Depressive patients is the high-risk group committed suiside, and in patient's morbidity to convalescence, there is the danger of suicide all the time.The identifying and diagnosing rate of depression is very low, and effective cure rate is also very low.Existing antidepressant Western medicine is mainly: tricyclic antidepressants (TCAs), selectivity 5-HT reuptake inhibitor (SSRIs), oxidase inhibitor (MAOIs), the toxic and side effects of their equal various degrees, and expensive, from Chinese medicine, thus research and develop new antidepressants there is important theoretical and practical significance.Our research shows that Radix Et Rhizoma Rhei micropowder has significant antidepressant activity to pharmacology's depression model.
The main aspect that medicine is different from natural drug is exactly that " Processing methods " uses afterwards, and the traditional Chinese medical science is particular about " life of medicine is ripe ", " raw ripe different use " very much when using drugs to form a prescription.The raw ripe decoction pieces of Chinese medicine not only there occurs change in the property of medicine and profile, and also there occurs change in chemical composition and pharmacological action.Radix Et Rhizoma Rhei, as an important processed product of Radix Et Rhizoma Rhei, is not only subject to doctor and widely uses, and also have certain discussion to its processing action in document.Sun Simiao points out Radix Et Rhizoma Rhei suitable " the raw use of real person, empty person's wine steams " in " silver-colored Nereid is micro-".Ming sieve Zhou Yan, ZHANG Jie bin etc. also think that valetudinarian, invalid uses after answering wine to cook again." danxi's experiential therapy " is said, Radix Et Rhizoma Rhei " raw with then logical the intestines and stomach heap soil or fertilizer over and around the roots is hot, ripe use then separates all sore eliminating heart-fires ".Dou Hanqing thinks that the Radix Et Rhizoma Rhei concocted with the method for " nine leachings nine are steamed nine and shone " has effect of " having benefit in rushing down ".As can be seen here, Radix Et Rhizoma Rhei has raw ripe different characteristic, and doctor admits this viewpoint mostly at all times.Comprehensive Radix Et Rhizoma Rhei concocts object roughly has two in fact, and one is relax the side effect of rushing down the lower and gas that injures one's stomach, impairment of YIN blood, and two is change property of medicine trend, strengthens or outstanding heat-clearing and toxic substances removing, blood circulation invigorating efficacies.Have no report Radix Et Rhizoma Rhei and anthraquinone component and stilbene methods of glycosides thereof and there is antidepressant effect.
Summary of the invention
The object of this invention is to provide containing the purposes of Radix Et Rhizoma Rhei micropowder as prevention and therapy antidepressant agents, with Radix Et Rhizoma Rhei micropowder for active component manufacture control antidepressant agents.Radix Et Rhizoma Rhei micropowder has the little feature of toxicity, and has obvious mitigation to degradation under the learning memory of depression secondary.Radix Et Rhizoma Rhei micropowder or using it as active component the Pharmaceutical composition etc. of composition comprise for the preparation of prevention or treatment the medicine of the various depressive symptoms of depression that endogenous depression, reactive depression, masked depression, drug-induced secondary depression, climacteric or postpartum depression, cerebral trauma or apoplexy bring out and depressive neurosis application and for Patients with Diabetes Accompanied by Depression, and decline for the preparation of the insecondary learning and memory that prevention and therapy depression causes, the application in the medicine of the symptoms such as anhedonia.
The Radix Et Rhizoma Rhei micropowder that the present invention realizes its goal of the invention is obtained by following approach:
Radix Et Rhizoma Rhei micropowder derives from the dry rhizome of polygonaceae plant Rheum officinale RheumofficinaleBaill.; Concocting method is: 1) Radix Et Rhizoma Rhei scrapes off crust, cuts sheet or block, obtains rhubarb tablets or block, 2 at 30 DEG C of-50 DEG C of oven drying at low temperatures) concoct: mix thoroughly with yellow wine, the yellow wine 30kg of every 100kg rhubarb tablets or block 15-16%; Vexed 1.5 are littlely sucked up to wine, put in high-pressure sterilizing pot and steam 6 hours, take out, dry; 3) preparation of Radix Et Rhizoma Rhei micropowder: get process of preparing Chinese medicine gained Radix Et Rhizoma Rhei medical material and throw in super micron mill, pulverize 5-8min, obtaining final product, particle diameter is: 50-78 μm.
Further detection can find, concocts in the Radix Et Rhizoma Rhei micropowder of gained containing Anthraquinones compound, stibene glucoside type compound and polysaccharide.
It is pharmaceutical composition and the pharmaceutical dosage form thereof of active component that another object of the present invention is to provide containing Radix Et Rhizoma Rhei micropowder or its active component anthraquinone component and stilbene methods of glycosides.
Radix Et Rhizoma Rhei micropowder prepare the wherein said Radix Et Rhizoma Rhei micropowder of the application in antidepressant agents derive from Radix Et Rhizoma Rhei medical material micronizing after powder.There is provided a kind of pharmaceutical composition of Cure of depression, it contains Radix Et Rhizoma Rhei micropowder is active component, adds the oral preparation of Chinese traditional medicinal that pharmaceutically acceptable adjuvant or complementary composition are prepared from.
Zoopery shows, medicine of the present invention can targetedly for prevention and therapy endogenous depression or/and reactive depression or/and masked depression or/and drug-induced secondary depression or/and climacteric or postpartum depression or/and the depression that brings out of cerebral trauma or apoplexy or/and depressive neurosis medicine in purposes, determined curative effect, without additive and dependency, without obvious toxic and side effects.
Detailed description of the invention
Zoopery is below to further description of the present invention, but and does not mean that any limitation of the invention.
Laboratory animal: male Kunming system SPF level mice, 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.Accept 12h illumination/12h every day dark, periodicity of illumination is 8:00-20:00, laboratory temperature 20 ± 2 DEG C, humidity 60%, and animal can absorb standard feed and cleaning water voluntarily, and International Laboratory Animal ethics requirement is observed in zoopery.
Medicine:
Rhubarb medicinal material, purchased from new Flos Nelumbinis Radix Et Rhizoma Rhei planting base, Chengdu, Sichuan, is concocted the first penetrating judgment of teaching and research room Lu through Chengdu University of Traditional Chinese Medicine and is awarded the dry rhizome being accredited as polygonaceae plant Rheum officinale RheumofficinaleBaill..Concocting method is, Radix Et Rhizoma Rhei: scrape off crust cuts sheet or block, and low temperature (30 DEG C-50 DEG C) is dried; Radix Et Rhizoma Rhei: get Radix Et Rhizoma Rhei sheet or block appropriate, mix thoroughly, put wine and be sucked, put in high-pressure sterilizing pot and steam 6 hours for vexed 1.5 hours with yellow wine, takes out, dry.Every 100kg rhubarb tablets or block, with yellow wine 30kg (wine degree: 15-16%).
The preparation of Radix Et Rhizoma Rhei micropowder: get process of preparing Chinese medicine gained Radix Et Rhizoma Rhei medical material and throw in super micron mill, pulverize 5-8min, to obtain final product.Particle diameter is: 50-78 μm.
Fluoxetine (hydrochloric acid chlorine western spit of fland capsule) Li Lai Suzhou pharmaceutical Co. Ltd
Reserpine injection Guangdong Bangmin Pharmaceutical Co., Ltd.
0.9% normal saline Kelun Pharm Ind Co., Ltd., Sichuan
Experimental program:
1 mouse experiment
1.1 behavioral despair (behaviouraldespair, BD) depression models
BD model comprises forced swim test (ForcedSwimmingTest, and tail-suspention test (TailSuspensionTest FST), TST), its theoretical basis is: under the stressed condition of forced swimming or outstanding tail, desperate performance is there is in animal via after struggling, i.e. motionless state, and antidepressant can shorten the dead time of animal.The former be draped using animal with the dead time of animal in water, the latter after dead time as evaluating the index of Degree of Depression.Behavioristics due to this type of animal pattern changes and almost can be reversed by clinical most antidepressants applied now, there is responsive, easy feature, therefore be usually used in the rapid screening of antidepressants, be that current antidepressant drug screens the animal model be most widely used.But affect the many factors of BD model, the time etc. of the judgement of state as motionless in animal, the quiet degree of environment and experiment all may have influence on the accuracy of experimental result.
Experimental technique:
KM mice 100 random packet are Normal group, the high, medium and low dosage group of Radix Et Rhizoma Rhei micropowder suspension, positive drug group, amount to 5 groups, and often organize 20 animals, each treated animal dosage regimen is as follows:
(1) Normal group: oral to distilled water;
(2) Radix Et Rhizoma Rhei micropowder suspension high dose group 5g/kg.d;
(3) dosage group 2.5g/kg.d in Radix Et Rhizoma Rhei micropowder suspension;
(4) Radix Et Rhizoma Rhei micropowder suspension low dose group 1.25g/kg.d
(5) prozac group: 5mg/kg.d
Tail-suspention test (TailSuspensionTest, TST)
Each treated animal gastric infusion every day 1 time, successive administration 7 days, last day, positive controls was to amitriptyline hydrochloride tablet aqueous solution, after administration 30min, mouse tail is about 2cm place clip apart from end fix, mice is hung upside down in outstanding boot, and its head is about 5cm at the bottom of case.Mice gets started observation after hanging 2min, observes and continues 6min, the dead time (mice aloft stops struggling, or only has tiny limb motion) of mice in this 6min accumulative.
Forced swim test (ForcedSwimmingTest, FST)
After each group of mice last gives relative medicine or distilled water 30min, mouse head is put into the swimming cup of diameter 16cm, depth of water 18cm down, water temperature 25 ± 2 DEG C, immediately with the dead time in stopwatch record mice 6min.
Each group of table 1 is on the impact of dead time in Tail suspension test and in forced swim test
Note: with Normal group Bi compare ﹡ P<0.05 ， ﹡ ﹡ P<0.01; #P<0.05 is compared, ##P<0.01 (lower same) with fluoxetine group.
From the above experimental results, Radix Et Rhizoma Rhei micropowder high dose group, has obvious antidepressant effect to behavioral despair depression model.
1.2 impacts on drug-induced depressive state
The symptomes complice that the compounds such as reserpine bring out animal by monoamine transmitters in exhaustion brain mainly comprises: temperature decline, blepharoptosis and movable suppression.The generation of these symptoms may reduce monoamine transmitters in brain with reserpine. especially 5-hydroxy tryptamine (5-HT), and the result that supervention 5-HT receptor sensitivity changes.Monoamine transmitters system mainly comprises 5-HT system, NE system and dopamine (DA) system, plays an important role in the pathogenesis of depression.5-HT in Brain of Patients with Depression and cerebrospinal fluid, 5-HI-AA, NE equal size is all low than normal person.5-HT relates to the adjustment of emotion, sleep, vigilance, memory and appetite etc., and NE deficiency then can cause mental retardation.Monoamine oxidase, MAO (MAO) is the important inactivator of monoamine transmitters (5-HT, NE, DA), if this enzyme is suppressed, monoamine transmitter contents in brain will be made to increase, and this has positive effect to improving depression.In 1950's, people, when observing the curative effect of antihypertensive reserpine, find about have this medicine of patient's long-term taking of 10-15% to produce depressive symptom.Pharmaceutical research display afterwards, the monoamine neurotransmitter in teleneuron vesicle is exhausted in the basic pharmacological action of reserpine, thus propose the monoamine hypothesis of depression. thinking that synaptic space monoamine neurotransmitter reduces is the depressed mechanism occurred, and antidepressants are by blocking monoamine-reuptake or suppressing monoamine oxidase, MAO (MAO), mediator metabolism is made to reduce and play antidepressant effect.
Experimental technique:
KM mice 120 random packet are Normal group, model group, fluoxetine group, the high, medium and low dosage group of Radix Et Rhizoma Rhei micropowder, amount to 6 groups, and often organize 20 animals, each treated animal dosage regimen is as follows:
(1) Normal group: oral to distilled water;
(2) Radix Et Rhizoma Rhei micropowder suspension high dose group 5g/kg.d;
(3) dosage group 2.5g/kg.d in Radix Et Rhizoma Rhei micropowder suspension;
(4) Radix Et Rhizoma Rhei micropowder suspension low dose group 1.25g/kg.d
(5) prozac group: 5mg/kg.d
(6) model group: reserpine 1mg/kg.d
The each group of continuous gavage distilled water of mice or relative medicine 6 days, except normal group, each group is given reserpine 1mg/kg, blepharoptosis after 60min, temperature decline after 180min, movablely to suppress.After mice last administration next day, 30min puts into mice open field test case, adapts to 2min, observes level, the Vertical movements number of times of mice in 4min subsequently, namely creep grid number and number of times of standing.
Each group of table 2 to be creeped grid number and the impact of number of times of standing on mice open field test
Note: compare with model group
△p<0.05 (lower same)
Mice autonomic activities is tested
Experimental technique is the same.
The each group of continuous gavage distilled water of mice or relative medicine 6 days, except normal group, each group is given reserpine 1mg/kg, blepharoptosis after 60min, temperature decline after 180min, movablely to suppress.After mice last administration next day, 30min puts into mice autonomic activities instrument, the movable number of times in record 5min.
Table 3 each group of impact on mice autonomic activities number of times
From the above experimental results, the antidepressant effect of Radix Et Rhizoma Rhei micropowder and monoamine mechanism irrelevant.
2 rat experiments
Chronic unpredictable sexual stimulus (CUMS) model
After the rat adaptability that purchase comes is fed one week, after weighing the body weight of experimental rat, be divided into 4 groups at random, often organize 6; Be respectively: normal group, normal administration group, model group and model administration group.The chronic unpredictable sexual stimulus (CUMS) that model group and model administration group carry out 4 cycles sets up depression model, is proceeding to the 4th cycle gastric infusion.Each treated animal dosage regimen is as follows:
(1) Normal group: oral to distilled water;
(2) normal administration group 2.5g/kg.d;
(3) model group is oral gives distilled water;
(4) model administration group 2.5g/kg.d
2.1 open field tests (OPENFIELDTEST)
Comparatively dim and comparatively quietly local (evening about 20) at light, single rat is put into the center grid of open field test device, start timing, the level of observing in rat 5min is passed through grid lattice number (rat 3 claws all enter in same grid and get a point) and is counted horizontal score and rat and stand that number of times (stand number of times by rat two rear solid ends, stand and once get a point) count vertical score, after the experiment action often having observed a rat, with the alcoholic solution cleaning device of 70%, avoid the test result of next rat of odor impact of a rat, by to be analyzed on minute book with vertical call for the horizontal score of each rat, result is as follows
The horizontal score of table 4 rat open field test and vertical score
2.2 sucrose solution preference test (SUCROSEPREFEREENCETEST; SPT)
The only cage of rat is raised, symmetrical random storing two water bottles in rearging cage, and 1% sucrose solution of splendid attire equivalent inside water bottle, gives rat 1% aqueous sucrose solution of 48 hours, and then prohibits water 16 hours to each rat; Prohibit water after 16 hours, one of them water bottle in large mouse cage is changed to distilled water, namely the distilled water of the water bottle in large mouse cage, one is 1% sucrose solution of the distilled water configuration filling equivalent, and the gross mass of weigh with scale these two water bottles and solution is also recorded on minute book; After 1 hour, take off these two water bottles and the quality of weigh with scale water bottle and solution be recorded in experiment on this, 1% aqueous sucrose solution consumed using rat relative to the percentage ratio of the amount of the total intake liquid of rat as the preference of rat to sucrose.In this experimentation, in order to avoid because the metabolism of jejunitas process influence matched group of cutting off the water supply in experimentation as far as possible, Normal group is only tested baseline values.
The sucrose solution preference of table 5 rat sucrose solution preference test
2.3 rat forced swimming test
Single rat is put into homemade tank, the degree of depth of the water in experimental trough is 30cm, the temperature of water is 25 ± 2 DEG C, the time that rat puts into tank is altogether 6min, with the non-swimming time of stopwatch record rat in rear 4min in pond (with rat in water only with small limb motion, only head is kept to be index on the water surface), record the non-swimming time of each rat.
Table 6 rat forced swimming test
Above experimental result shows: Radix Et Rhizoma Rhei micropowder has obvious antidepressant effect on rat CUMS model.
Claims (7)
1. the purposes of Radix Et Rhizoma Rhei micropowder in preparation medicament for treatment of depression, with Radix Et Rhizoma Rhei micropowder for active component manufacture control and prevention of depression medicine.
2. purposes according to claim 1, is characterized in that, described Radix Et Rhizoma Rhei micropowder derives from the dry rhizome of polygonaceae plant Rheum officinale RheumofficinaleBaill.; Concocting method is: 1) Radix Et Rhizoma Rhei scrapes off crust, cuts sheet or block, obtains rhubarb tablets or block, 2 at 30 DEG C of-50 DEG C of oven drying at low temperatures) concoct: mix thoroughly with yellow wine, the yellow wine 30kg of every 100kg rhubarb tablets or block 15-16%; Vexed 1.5 are littlely sucked up to wine, put in high-pressure sterilizing pot and steam 6 hours, take out, dry; 3) preparation of Radix Et Rhizoma Rhei micropowder: get process of preparing Chinese medicine gained Radix Et Rhizoma Rhei medical material and throw in super micron mill, pulverize 5-8min, obtaining final product, particle diameter is: 50-78 μm.
3. purposes according to claim 2, is characterized in that: containing Anthraquinones compound, stibene glucoside type compound and polysaccharide in described Radix Et Rhizoma Rhei micropowder.
4. purposes according to claim 1, is characterized in that: the medicine of described control depression prepare prevention and therapy endogenous depression or/and reactive depression or/and masked depression or/and drug-induced secondary depression or/and climacteric or postpartum depression or/and the depression that brings out of cerebral trauma or apoplexy or/and depressive neurosis medicine in purposes.
5. purposes according to claim 1, the medicine of described control depression declines or/and purposes in anhedonia disease drug preparing insecondary learning and memory that prevention and therapy depression causes.
6. a pharmaceutical composition for Cure of depression, is characterized in that, is active component containing Radix Et Rhizoma Rhei micropowder, adds the Chinese medicine preparation that pharmaceutically acceptable adjuvant or adjuvanticity composition are prepared from.
7. pharmaceutical composition according to claim 6, the oral formulations described in it is tablet, capsule, granule or oral liquid.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110898109A (en) * | 2019-12-09 | 2020-03-24 | 普济生物科技（台州）有限公司 | Application of cooked rhubarb in preventing and treating depression |
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| CN101961326A (en) * | 2010-10-29 | 2011-02-02 | 西南交通大学 | Application of physcion in preparing medicines for treating depression |
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- 2015-12-29 CN CN201511004608.2A patent/CN105497160A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101961325A (en) * | 2010-10-29 | 2011-02-02 | 西南交通大学 | Application of emodin in preparation of drugs for treating depression |
| CN101961326A (en) * | 2010-10-29 | 2011-02-02 | 西南交通大学 | Application of physcion in preparing medicines for treating depression |
Non-Patent Citations (1)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110898109A (en) * | 2019-12-09 | 2020-03-24 | 普济生物科技（台州）有限公司 | Application of cooked rhubarb in preventing and treating depression |
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