CN104257790B - A kind of new application of FUFANG ZAOREN JIAONANG - Google Patents

A kind of new application of FUFANG ZAOREN JIAONANG Download PDF

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CN104257790B
CN104257790B CN201410514668.8A CN201410514668A CN104257790B CN 104257790 B CN104257790 B CN 104257790B CN 201410514668 A CN201410514668 A CN 201410514668A CN 104257790 B CN104257790 B CN 104257790B
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jiaonang
zaoren
fufang
depression
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CN104257790A (en
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付立家
付建家
马筠
赵敏姿
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Beijing Asia East Bio Pharmaceutical Co Ltd
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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)
    • A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
    • A61K36/725—Ziziphus, e.g. jujube
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

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Abstract

The present invention relates to the new application of FUFANG ZAOREN JIAONANG, be specifically related to the application in the medicine of preparation treatment depression.The present invention finds through experiment: FUFANG ZAOREN JIAONANG can treat mild depression, manic-depressive illness or desperate type depression, evident in efficacy, and is better than being used alone antacid Semen Ziziphi Spinosae and rotundine.

Description

A kind of new application of FUFANG ZAOREN JIAONANG
Technical field
The present invention relates to the new application of FUFANG ZAOREN JIAONANG, be specifically related to FUFANG ZAOREN JIAONANG in terms for the treatment of depression New application.
Background technology
Depression is also known as depressive disorder, low as main clinical characteristics with notable and lasting mental state, is mood disorders Main Types.
So far, the cause of disease of depression is the most unclear, but certainly, biological, psychology and all many-sides of social environment Factor take part in the pathogenic process of depression.Biological factor relates generally to heredity, neural biochemistry, neuroendocrine, nerve again The aspects such as life；It is premorbid personality feature that the psychology in close relations with depression is susceptible to suffer from quality, such as depressed makings.Manhood meets with Irritable life events, is the important trigger condition of the paralepsy causing occurring having clinical meaning.But, the above Factor is not individually to work, and emphasizes the reciprocal action between nature-nurture or stressors and this friendship at present The appearance time point of interaction has important impact in depression generating process.
Major depression patient there will be pessimistic and worldweary, desperate, hallucination vain hope, inappetence, hypofunction with sternly The suicidal attempt of weight, even suicide.Human health is constituted a serious threat, it is therefore necessary to pay much attention to, treat in time, its In:
Manic-depressive illness is the surging or low mental disorder disease being characterized of a kind of exception with emotion, its cause of disease It is still not clear, has manic state and two kinds of main performances of depressive state concurrently, can be in same patient interval alternate repetition outbreak, it is possible to Be main recurrent exerbation with a kind of state, have periodically and can palliative, intermission patient's ergasia is completely normal, the most not Performance personality defect.
Lasting sorrow, anxiety or mental state are hollow, to LOM interest interested, excessive sobbing, uneasiness And impatience, note and the ability made decision declines, deficient in energy, want to die or the idea committed suiside or trial, guilty sense, helplessness And/or hopeless sense increase, due to feed increase or reduce cause body weight and/or appetite change, sleep change, Social Withdrawal, standard The somatization (such as chronic pain, headache) that treatment still can not be alleviated.
The antipyretic of existing market is usually Western medicine, and curative effect is not notable, and side effect is the biggest.Some Chinese patent medicine has one Fixed effect, but the problem that there is curative effect and side effect.
FUFANG ZAOREN JIAONANG, also has referred to as compound Semen Ziziphi Spinosae capsule, and its active component is Semen Ziziphi Spinosae (system), left-handed Rhizoma Corydalis B prime, adjuvant is starch, and primary efficacy is tranquilizing by nourishing the heart.It is applicable to irritability, insomnia, dreaminess, palpitation with fear.The most left-handed Rhizoma Corydalis Suo Yisu is uterine contraction pain, tonicity insomnia, spasmodic cough after gastric ulcer and the pain of duodenal ulcer, menstrual pain, childbirth Cough, Semen Ziziphi Spinosae treatment insomnia.
There is a patent report:
A kind of Chinese medicine preparation for treating insomnia of CN200610078947.X (Publication No. CN1872186A) is multiple Side's capsule of Chinese date kernel, it is characterised in that it is made up of Semen Ziziphi Spinosae and rotundine.
Report about FUFANG ZAOREN JIAONANG or the purposes of Semen Ziziphi Spinosae is as follows:
Li Rongheng etc. (are published in that " Chengdu Chinese medicine is big in the clinical research of compound Semen Ziziphi Spinosae ANSHEN JIAONANG treatment of insomnia patients Learn journal " phase nineteen ninety-five 01) in disclose compound Semen Ziziphi Spinosae ANSHEN JIAONANG and can treat insomnia, effect is better than Cinnabar Sedative Pill.
Huang Shijing " Semen Ziziphi Spinosae treatment depression research with application " (be published in global Chinese medicine, the 9th phase in 2013 700-703 page, page totally 4) disclose Semen Ziziphi Spinosae application in treatment depression.
Have not yet to see the FUFANG ZAOREN JIAONANG report for manic depressive illness.
Summary of the invention
It is an object of the invention to provide the new application of a kind of FUFANG ZAOREN JIAONANG.
The invention provides FUFANG ZAOREN JIAONANG application in the medicine of preparation treatment depression.
Described depression includes desperate type depression, manic-depressive illness or mild depression.
Preferably, described depression is desperate type depression or manic-depressive illness.
Further preferably, described depression is manic-depressive illness.
Described FUFANG ZAOREN JIAONANG is commercially available purchase.
When present invention also offers above-mentioned application, plan consumption 1-3 tablet/time of people, 2-3 times/day.
The new application of the FUFANG ZAOREN JIAONANG that the present invention provides has the advantage that
1, prior art is write exactly Semen Ziziphi Spinosae there is the effect for the treatment of depression, but cannot learn that FUFANG ZAOREN JIAONANG is No have treatment depression, and especially desperate type and manic type belong to the intense evolution of depression.
2, find through experiment: FUFANG ZAOREN JIAONANG can treat mild depression, manic-depressive illness, desperate type depression Disease, evident in efficacy, and be better than being used alone Semen Ziziphi Spinosae and rotundine.
Detailed description of the invention
Following example are used for illustrating the present invention, but are not limited to the scope of the present invention.
Experimental example 1: the FUFANG ZAOREN JIAONANG impact on behavioral despair depression model mice
1, laboratory animal: the SPF level female KM kind mice of body weight 18-22g.
2, experiment packet: mice 60, is randomly divided into 6 groups: blank group, antacid Semen Ziziphi Spinosae group, rotundine Group, positive drug group (amitriptyline), FUFANG ZAOREN JIAONANG high dose group, FUFANG ZAOREN JIAONANG low dose group, often group 10.
3, experimental technique: every day, blank group gavage normal saline, positive drug group gavage Ah rice replaced in 08:00 gavage Woods solution, antacid Semen Ziziphi Spinosae group gavage antacid Semen Ziziphi Spinosae solution, rotundine group gavage rotundine solution, respectively Give antacid Semen Ziziphi Spinosae 4g/kg body weight, rotundine 0.9g/kg；FUFANG ZAOREN JIAONANG group gavage respective concentration compound recipe Fructus Jujubae Cannabis capsule aqueous solution, above each group, gavage capacity is 0.2ml/10g, continuous 8d.
7d, carries out tail-suspention test, the dead time of mice in 5min after observation.
4, result: be shown in Table 1
Table 1 FUFANG ZAOREN JIAONANG impact (x ± s) n=10 on Tail suspension test
Group Dosage (g/kg) Dead time relative value (%)
Blank group —— 100.00±35.57
Antacid Semen Ziziphi Spinosae group 4 85.43±45.86*
Rotundine group 0.9 79.36±32.39*
Positive drug group 0.01 45.23±47.12**
FUFANG ZAOREN JIAONANG high dose group 4 51.01±26.46**#&
FUFANG ZAOREN JIAONANG low dose group 2 63.45±30.23**#&
Note: compare with blank group,*P < 0.05,**P<0.01；Compared with antacid Semen Ziziphi Spinosae group,#P<0.05；Prolong with left-handed Rhizoma Corydalis B prime group is compared,&P<0.05。
Table 1 result shows: compare with blank group, tests each group and all can shorten mouse forced swimming test in various degree With the dead time (P < 0.01, P < 0.05) of tail-suspention test, respectively compared with antacid Semen Ziziphi Spinosae group and rotundine group, multiple Side's capsule of Chinese date kernel substantially shortens the dead time (p < 0.05) of mouse forced swimming test and tail-suspention test.
Result shows: FUFANG ZAOREN JIAONANG can significantly improve desperate type depression, especially improves desperate type depression and leads Cause desperate mental status, there is synergy.
Experimental example 2: the FUFANG ZAOREN JIAONANG research to manic rat
1, laboratory animal: SD rat, SPF level, male and female half and half, body weight 160-200g.
2, experiment packet and experimental technique: 60 rats, is randomly divided into blank group, model group, antacid after raising 1 week Semen Ziziphi Spinosae group, rotundine group, sodium valproate group, FUFANG ZAOREN JIAONANG group, often group 10.
Sleep deprivation method (MMPM) is used to set up manic model.Blank group and model group do not do any intervention；Sodium valproate Group, gives sodium valproate 300mg/kg body weight, is dissolved in gavage in 2m1 pure water, 1 times/day, antacid Semen Ziziphi Spinosae group, left-handed Rhizoma Corydalis second Element group dosage is 3g/kg with embodiment 1, FUFANG ZAOREN JIAONANG group dosage, gavage capacity is 0.2ml/10g.Water Environmental treatment observes the spirit of each group of rat, behavior, record disengaging water environment to the time entering sleep for the first time after within 7 days, terminating (i.e. Sleep latency) and 12 hours food-intakes.
3, experimental result:
Compare with model group, FUFANG ZAOREN JIAONANG group, sodium valproate group, antacid Semen Ziziphi Spinosae group, rotundine group Body weight, 12h food-intake and emotion excitement difference the most statistically significant (P < 0.01, P < 0.05), prompting sodium valproate and compound recipe Capsule of Chinese date kernel group can alleviate mania to body weight, 12h food-intake and the impact of emotion excitement；With antacid Semen Ziziphi Spinosae group, left-handed Rhizoma Corydalis Suo Yisu group is respectively compared, FUFANG ZAOREN JIAONANG group body weight, 12h food-intake and emotion excitement difference the most statistically significant (P < 0.05)。
Result shows: FUFANG ZAOREN JIAONANG group can be obviously improved manic-depressive illness, especially manic-depressive illness and cause Sleep disorder, and there is synergy.
Experimental example 3: the FUFANG ZAOREN JIAONANG comprehensive study to depression
One cardinal symptom of depression is the minimizing of motivational behavior.Have selected 3 kinds of pharmacological experiments to confirm this Chinese medicine The antidepressant effect of complex.
1, experimental principle
1.1 Tail suspension tests: in Tail suspension test model, outstanding tail mice is for overcoming abnormal position and work of struggling Dynamic, this is the motivational behavior of mice；But activity is to after certain time, occurs that discontinuity is motionless, the disappointed state of display.Referred herein Immobility reflect one and be referred to as " behavioral despair and distortion " or " to suppressing the failure that environment adapts to " state, be a kind of Passive absence of motivation despair state；To measure the dead time of mice after outstanding tail a period of time, little mouse-anti is pressed down evaluating medicine Strongly fragrant curative effect；
1.2 forced swim test: in mouse forced swimming test model, mice is forced in swimming in the space of a limitation, First they show the motivational behavior struggled and make an attempt at escaping；Feel that it is impossible for escaping, and the most no longer struggles and swims subsequently Dynamic, only head is surfaced, limbs are floating, maintain a kind of motionless state, are in the motionless of one " desperate ".Force to measure The dead time of mice after swimming a period of time, evaluate the curative effect of antidepressants.
The depression test that 1.3 antagonism are caused by reserpine: the minimizing of monoamine neurotransmitter can frequently result in depressed, health The change of power dropping, appetite and libido, causes depressive and anxiety neurosis.Reserpine is a kind of vesicle reuptake inhibitor, it Make mediator stay outside vesicle, easily degraded by monoamine oxidase, MAO, so that NE, 5-HT etc. exhaust, thus cause depressive symptom.Abdominal cavity After injection reserpine 60min, observe the number of mice blepharoptosis, in order to judge the curative effect of antidepressants.
2, specific experiment method
2.1 Tail suspension tests:
2.1.1 laboratory animal: 60 male mouse of kunming, body weight 28 ± 2g.
2.1.2 test packet: 60 mices, be randomly divided into 6 groups, i.e. give isopyknic normal saline group, antacid Semen Ziziphi Spinosae Group, rotundine group, low dose group, middle dosage group and Chinese medicine high dose group, wherein:
Dosage expression way is compound recipe for (oral crude drug grams/animal kg body weight) FUFANG ZAOREN JIAONANG low dose group Capsule of Chinese date kernel 2g/kg, middle dosage group is 5g/kg, and high dose group is 10g/kg, and the dosage of antacid Semen Ziziphi Spinosae group is 6.8g/Kg, The dosage of rotundine group is 1.5g/Kg, often group 10.
2.1.3 experimental technique: adapt to environment after a week, equal gastric infusion, every day 1 time, successive administration 7 days, and in experiment Within 1st, 3,7 day, test.Before experiment, 24h animal list cage is raised, and water is can't help in fasting.Each treated animal is administered after 1 hour in last, With adhesive plaster, mouse tail is being sticked at outstanding tail balance bracket at tail point 2cm, do not making mouse tail distortion fold so that it is head is downward Hang in upside down shape, head distance desktop 15cm,.Every mouse tail suspension 6min, front 2min adapts to, adding up in 4min after record Dead time (fixed finger mice all limbs in addition to breathing are the most motionless).
2.1.4 experimental result: be shown in Table 2.
The impact on the mouse tail suspension dead time of the table 2 various dose Chinese medicine composition
Note: compare with blank group,***P < 0.001,**P < 0.01,*P<0.05；Compared with antacid Semen Ziziphi Spinosae group,##P< 0.01,#P<0.05；Compared with rotundine group,&&P < 0.01,&P<0.05。
Table 2 result shows: compared with normal saline group, test each group all have in various degree shorten tail-suspention test motionless Time (P < 0.001, P < 0.01, P < 0.05)；Respectively compared with antacid Semen Ziziphi Spinosae group, rotundine group, basic, normal, high dose Amount group has the dead time (P < 0.01, P < 0.05) shortening tail-suspention test in various degree.
Result shows: FUFANG ZAOREN JIAONANG has the effect that the desperate type of suppression is depressed, and has synergy.
2.2 mouse swimming test
2.2.1 laboratory animal: male mouse of kunming, body weight 28 ± 2g.
2.2.2 testing packet: 60 mices, be randomly divided into 6 groups, often group 10, is grouped same 2.1.2.
2.2.3 experimental technique: before swim test experiment, 24h animal carries out swimming instruction 15 minutes, and single cage raising, fasting Can't help water.The single diameter about 18cm that only puts into of mice after being administered 1h during experiment, depth of water 18cm, the circular appearance of water temperature 25 ± 1 DEG C In device, accumulative dead time in 4min after adapting to start after 2min to calculate (floating motionless state, only exposes nostril and keeps breathing, Extremity paddling once in a while is unlikely to sink with holding health).
Swimming detection time same 2.1.3
2.2.4: experimental result: be shown in Table 3
The impact on mice non-swimming time of the table 3 various dose Chinese medicine composition
Note: compare with blank group,***P < 0.001,**P < 0.01,*P<0.05；Compared with antacid Semen Ziziphi Spinosae group,###P< 0.001,##P < 0.01,#P<0.05；Compared with rotundine group,&&&P < 0.001,&&P < 0.01,&P<0.05。
Table 3 result shows: compared with normal saline group, test each group all have in various degree shorten mice swimming motionless Time (P < 0.001, P < 0.01, P < 0.05), respectively compared with antacid Semen Ziziphi Spinosae group, rotundine group, basic, normal, high dose Amount group has the dead time (P < 0.01, P < 0.05) shortening mice swimming in various degree.
The sagging experiment in upper eyelid caused by 2.3 reserpines:
2.3.1 laboratory animal: male mouse of kunming, body weight 28 ± 2g.
2.3.2 test packet: mice 770, be randomly divided into 7 groups (i.e. normal group, reserpine group, antacid Semen Ziziphi Spinosae group, left-handed Tetrahydropalmatine group, low dose group, middle dosage group, high dose group), often 10 (antacid Semen Ziziphi Spinosae group, rotundines of group Group, low dose group, middle dosage group, 5 groups of same 2.1.2 of dosage such as high dose group).
2.3.3 experimental technique:
Adapt to environment after a week, equal gastric infusion, every day 1 time, successive administration 7 days, test in the 7th day.
Test experiments normal group on same day intraperitoneal injection of saline 4mg/kg, remaining 4 groups 1h lumbar injection profits after being administered The flat 4mg/kg of blood, observes rathole blepharoptosis degree, and adds up in the way of marking after 1h.
Scoring criterion is: widening the view completely is 0 point, and 1/4 eye closing is 1 point, and 1/2 eye closing is 2 points, and 3/4 eye closing is 3 points, completely Eye closing is 4 points.
2.3.4 experimental result: table 4.
Mice upper eyelid nutating action is marked by table 4 various dose Chinese medicine composition
Note: compare with blank group,**P < 0.01, compared with antacid Semen Ziziphi Spinosae group,#P < 0.05, with rotundine Compare by group,&P<0.05
Table 4 result shows: compared with normal group, and it is sagging that reserpine group significantly increases upper eyelid, it was demonstrated that modeling success；With Reserpine group is compared, each administration group the most in various degree decrease the sagging number in upper eyelid (P < 0.01, P < 0.05)；Respectively with Antacid Semen Ziziphi Spinosae group, rotundine group are compared, basic, normal, high dosage group have in various degree to decrease upper eyelid sagging Number (P < 0.05).
Experiment brief summary: FUFANG ZAOREN JIAONANG can treat mild depression, desperate type depression, has synergy.
Although, used general explanation, detailed description of the invention and test, the present invention made detailed retouching Stating, but on the basis of the present invention, can make some modifications or improvements it, this is apparent to those skilled in the art 's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed Scope.

Claims (1)

1. FUFANG ZAOREN JIAONANG application in the medicine of preparation treatment depression, it is characterised in that described depression is manic Type depression.
CN201410514668.8A 2014-09-29 2014-09-29 A kind of new application of FUFANG ZAOREN JIAONANG Active CN104257790B (en)

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CN106466416A (en) * 2015-08-20 2017-03-01 山东金诃药物研究开发有限公司 Application in preparation medicament for treatment of depression for the compound recipe Rhizoma Gymnadeniae ball
CN113521184A (en) * 2021-07-29 2021-10-22 福建中医药大学 Composition for improving sleep quality

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