CN104257790A - Novel application of compound jujube kernel capsule - Google Patents

Novel application of compound jujube kernel capsule Download PDF

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CN104257790A
CN104257790A CN201410514668.8A CN201410514668A CN104257790A CN 104257790 A CN104257790 A CN 104257790A CN 201410514668 A CN201410514668 A CN 201410514668A CN 104257790 A CN104257790 A CN 104257790A
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depression
jiaonang
zaoren
fufang
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CN104257790B (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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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a novel application of a compound jujube kernel capsule and in particular relates to a novel application of preparing a medicament for treating depression. Found by experiments that the compound jujube kernel capsule can be used for treating mild depression, manic type depression or desperation type depression and is remarkable in curative effect, and the curative effect is superior to that of singly using a prepared spine date seed and l-tetrahydropalmatine.

Description

A kind of novelty teabag of FUFANG ZAOREN JIAONANG
Technical field
The present invention relates to the novelty teabag of FUFANG ZAOREN JIAONANG, be specifically related to the novelty teabag of FUFANG ZAOREN JIAONANG in Cure of depression.
Background technology
Depression is also known as depressive disorder, low for main clinical characteristics with remarkable and lasting mental state, is the main Types of mood disorders.
So far, the cause of disease of depression is also unclear, but certainly, and biological, psychology and all many factors of social environment take part in the pathogenic process of depression.Biological factor relates generally to the aspect such as heredity, neural biochemistry, neuroendocrine, neuranagenesis; It is premorbid personality feature that the psychology in close relations with depression easily suffers from quality, as depressed makings.Manhood meets with irritable life events, is the important trigger condition of the paralepsy causing occurring having clinical meaning.But these factors above are not work separately, emphasize reciprocal action between nature-nurture or stressors at present and thisly interactively occur that time point has important impact in depression generating process.
Major depression patient there will be pessimistic and worldweary, desperate, hallucination vain hope, inappetence, hypofunction with serious suicidal attempt, even suicide.Human health is constituted a serious threat, therefore must pay much attention to, treat in time, wherein:
Manic-depressive illness is the surging or low mental disorder disease for feature of a kind of exception with emotion, its cause of disease is still not clear, have manic state and depressive state two kinds of main manifestations concurrently, can in the outbreak of same patient's interval alternate repetition, also can a kind of state be main recurrent exerbation, have periodically and can palliative, intermission patient ergasia be completely normal, does not generally show personality defect.
Lasting sorrow, anxiety or mental state are hollow, to former interested LOM interest, excessive sobbing, uneasy and impatient, the ability noted and make decision declines, deficient in energy, want to die or the idea of committing suiside or trial, guilty sense, helplessness and/or hopeless sense increase, body weight and/or appetite change is caused because feed increases or reduces, sleep change, Social Withdrawal, the somatization (as chronic pain, headache) that standard care still can not be alleviated.
The antipyretic of existing market is generally Western medicine, and curative effect is not remarkable, and side effect is very large.Some Chinese patent medicine has certain effect, but there is the problem of curative effect and side effect.
FUFANG ZAOREN JIAONANG, also has and is called compound Semen Ziziphi Spinosae capsule, and its active component is Semen Ziziphi Spinosae (system), rotundine, and adjuvant is starch, and primary efficacy is tranquilizing by nourishing the heart.Be applicable to irritability, insomnia, dreaminess, palpitation with fear.Wherein rotundine is used for uterine contraction pain, tonicity insomnia, spasmodic cough etc. after the pain of gastric ulcer and duodenal ulcer, menstrual pain, childbirth, Semen Ziziphi Spinosae Cure for insomnia.
There is patent report:
CN200610078947.X (publication number is CN1872186A) a kind of Chinese medicine preparation being used for the treatment of insomnia---FUFANG ZAOREN JIAONANG, is characterized in that it is made up of Semen Ziziphi Spinosae and rotundine.
Report about the purposes of FUFANG ZAOREN JIAONANG or Semen Ziziphi Spinosae is as follows:
Li Rongheng etc. disclose compound Semen Ziziphi Spinosae ANSHEN JIAONANG in the clinical research (being published in " Chengdu University of Traditional Chinese Medicine's journal " phase nineteen ninety-five 01) of compound Semen Ziziphi Spinosae ANSHEN JIAONANG treatment of insomnia patients can Cure for insomnia, and effect is better than Cinnabar Sedative Pill.
Huang Shijing is " " (being published in global Chinese medicine, the 9th phase 700-703 page in 2013, totally 4 pages) discloses the application of Semen Ziziphi Spinosae in Cure of depression to the research and apply of Semen Ziziphi Spinosae Cure of depression.
Have not yet to see the report of FUFANG ZAOREN JIAONANG for manic depressive illness.
Summary of the invention
The object of this invention is to provide a kind of novelty teabag of FUFANG ZAOREN JIAONANG.
The invention provides the application of FUFANG ZAOREN JIAONANG in the medicine preparing Cure of depression.
Described depression comprises 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, the plan consumption 1-3 tablet/time of people, 2-3 times/day.
The novelty teabag of FUFANG ZAOREN JIAONANG provided by the invention has the following advantages:
1, write the effect that Semen Ziziphi Spinosae has Cure of depression in prior art exactly, but cannot learn whether FUFANG ZAOREN JIAONANG has Cure of depression, 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, evident in efficacy, and is better than being used alone Semen Ziziphi Spinosae and rotundine.
Detailed description of the invention
Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.
Experimental example 1: FUFANG ZAOREN JIAONANG is on the impact of behavioral despair depression model mice
The SPF level female KM kind mice of 1, laboratory animal: body weight 18-22g.
2, experiment grouping: mice 60, is divided into 6 groups at random: 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 organizes 10.
3, experimental technique: every day is in 08:00 gavage, blank group gavage normal saline, positive drug group gavage amitriptyline solution, antacid Semen Ziziphi Spinosae group gavage antacid Semen Ziziphi Spinosae solution, rotundine group gavage rotundine solution, give antacid Semen Ziziphi Spinosae 4g/kg body weight, rotundine 0.9g/kg respectively; FUFANG ZAOREN JIAONANG group gavage respective concentration FUFANG ZAOREN JIAONANG aqueous solution, above each group, gavage capacity is 0.2ml/10g, continuous 8d.
7d, carries out tail-suspention test, observes the dead time of mice in rear 5min.
4, result: in table 1
Table 1 FUFANG ZAOREN JIAONANG is on impact (x ± s) n=10 of 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; Compared with rotundine group, aMP.AMp.Ampp<0.05.
Table 1 result shows: compare with blank group, test the dead time (P<0.01 that each group all can be shortened mouse forced swimming test and tail-suspention test in various degree, P<0.05), compare with rotundine group with antacid Semen Ziziphi Spinosae group respectively, FUFANG ZAOREN JIAONANG obviously shortens the dead time (p<0.05) of mouse forced swimming test and tail-suspention test.
Result shows: FUFANG ZAOREN JIAONANG significantly can improve desperate type depression, especially improve that desperate type depression causes desperate mental status, there is synergy.
Experimental example 2: FUFANG ZAOREN JIAONANG is to the research of manic rat
1, laboratory animal: SD rat, SPF level, male and female half and half, body weight 160-200g.
2, experiment grouping and experimental technique: 60 rats, are divided into blank group, model group, antacid Semen Ziziphi Spinosae group, rotundine group, sodium valproate group, FUFANG ZAOREN JIAONANG group at random after raising 1 week, often organize 10.
Sleep deprivation method (MMPM) is adopted 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, rotundine group dosage are with embodiment 1, and FUFANG ZAOREN JIAONANG group dosage is 3g/kg,, gavage capacity is 0.2ml/10g.Water environment process terminates the spirit of rear observation each group of rat for 7 days, behavior, record depart from water environment to time (i.e. Sleep latency) and the 12 hours food-intake entering sleep for the first time.
3, experimental result:
Compare with model group, the excited difference of the body weight of FUFANG ZAOREN JIAONANG group, sodium valproate group, antacid Semen Ziziphi Spinosae group, rotundine group, 12h food-intake and emotion all has statistical significance (P<0.01, P<0.05), sodium valproate and FUFANG ZAOREN JIAONANG group is pointed out can to alleviate the impact of mania on body weight, 12h food-intake and emotion excitement; Compare respectively with antacid Semen Ziziphi Spinosae group, rotundine group, the excited difference of FUFANG ZAOREN JIAONANG group body weight, 12h food-intake and emotion all has statistical significance (P<0.05).
The sleep disorder that result display: FUFANG ZAOREN JIAONANG group obviously can improve manic-depressive illness, especially manic-depressive illness cause, and there is synergy.
Experimental example 3: FUFANG ZAOREN JIAONANG is to the comprehensive study of depression
A cardinal symptom of depression is the minimizing of motivational behavior.Have selected 3 kinds of pharmacological experiments to confirm the antidepressant effect of this Chinese herbal compounds.
1, experimental principle
1.1 Tail suspension tests: in Tail suspension test model, outstanding tail mice is for overcoming abnormal position and struggle activity, and this is the motivational behavior of mice; But after activity to certain hour, occur that discontinuity is motionless, show disappointed state.Here the immobility of indication reflects one and is referred to as " behavioral despair and distortion " or " failure to suppressing environmental adaptation " state, is a kind of desperate state of absence of motivation of passiveness; To measure the dead time of mice after outstanding tail a period of time, to evaluate medicine to the antidepressant curative effect of mice;
1.2 forced swim test: in mouse forced swimming test model, mice is forced in swimming in a space of limiting to, and first they show the motivational behavior of struggling and making an attempt at escaping; Feel that it is impossible for escaping subsequently, just no longer struggle and move about, only being surfaced by head, limbs are floating, maintain a kind of motionless state, are in the motionless of one " despair ".To measure the dead time of mice after forced swimming a period of time, evaluate the curative effect of antidepressants.
1.3 resist the depression test caused by reserpine: the minimizing of monoamine neurotransmitter usually can cause depressed, health power dropping, appetite and libido change, causes depressive and anxiety neurosis.Reserpine is a kind of vesicle reuptake inhibitor, and it makes mediator stay outside vesicle, is easily degraded by monoamine oxidase, MAO, thus makes the exhaustion such as NE, 5-HT, thus cause depressive symptom.After lumbar 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 grouping: 60 mices, are divided into 6 groups at random, namely 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 (oral crude drug grams/animal kg body weight) FUFANG ZAOREN JIAONANG low dose group is FUFANG ZAOREN JIAONANG 2g/kg, middle dosage group is 5g/kg, high dose group is 10g/kg, the dosage of antacid Semen Ziziphi Spinosae group is 6.8g/Kg, the dosage of rotundine group is 1.5g/Kg, often organizes 10.
2.1.3 experimental technique: after conforming a week, equal gastric infusion, every day 1 time, successive administration 7 days, and within the 1st, 3,7 days, test in experiment.Before experiment, the single cage of 24h animal is raised, and water is can't help in fasting.Mouse tail after 1 hour in last administration, is sticked at outstanding tail balance bracket at distance tail point 2cm place with adhesive plaster, does not make mouse tail distortion fold, its head is hung in upside down shape, head distance desktop 15cm downwards by each treated animal.Every mouse tail suspension 6min, front 2min adapts to, the accumulative dead time (fixed finger mice all limbs except breathing are all motionless) after record in 4min.
2.1.4 experimental result: in table 2.
Table 2 various dose Chinese medicine composition is on the impact of mouse tail suspension dead time
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, aMP.AMp.Amp &p<0.01, aMP.AMp.Ampp<0.05.
Table 2 result shows: compared with normal saline group, test the dead time (P<0.001, P<0.01, P<0.05) that each group all has shortening tail-suspention test in various degree; Respectively compared with antacid Semen Ziziphi Spinosae group, rotundine group, basic, normal, high dosage group has the dead time (P<0.01, P<0.05) of shortening tail-suspention test in various degree.
Result shows: FUFANG ZAOREN JIAONANG has the effect suppressing desperate type depression, and has synergy.
2.2 mouse swimming test
2.2.1 laboratory animal: male mouse of kunming, body weight 28 ± 2g.
2.2.2 test grouping: 60 mices, are divided into 6 groups at random, often organize 10, divide into groups same 2.1.2.
2.2.3 experimental technique: before swim test experiment, 24h animal carries out swimming instruction 15 minutes, and single cage is raised, and water is can't help in fasting.During experiment, the mice list after administration 1h is only put into diameter and be about 18cm, depth of water 18cm, in the bulge that water temperature is 25 ± 1 DEG C, start to calculate accumulative dead time (floating motionless state in rear 4min after adapting to 2min, only expose nostril to keep breathing, extremity once in a while paddling are unlikely to sink to keep health).
Swim same 2.1.3 detection time
2.2.4: experimental result: in table 3
Table 3 various dose Chinese medicine composition is on the impact of mice non-swimming time
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, aMP.AMp.Amp & &p<0.001, aMP.AMp.Amp &p<0.01, aMP.AMp.Ampp<0.05.
Table 3 result shows: compared with normal saline group, test the dead time (P<0.001 that each group all has shortening mice swimming in various degree, P<0.01, P<0.05), respectively compared with antacid Semen Ziziphi Spinosae group, rotundine group, basic, normal, high dosage group has the dead time (P<0.01, P<0.05) of 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 experiment grouping: mice 770, is divided into 7 groups of (i.e. normal group, reserpine groups at random, antacid Semen Ziziphi Spinosae group, rotundine group, low dose group, middle dosage group, high dose group), often organize 10 (antacid Semen Ziziphi Spinosae group, rotundine 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:
After conforming one 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, all the other 4 groups 1h lumbar injection reserpine 4mg/kg after administration, observe rathole blepharoptosis degree after 1h, and add up in the mode of marking.
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, and closing one's eyes completely is 4 points.
2.3.4 experimental result: table 4.
Table 4 various dose Chinese medicine composition is marked to mice upper eyelid nutating action
Note: compare with blank group, *p<0.01, compared with antacid Semen Ziziphi Spinosae group, #p<0.05, with rotundine by compared with group, aMP.AMp.Ampp<0.05
Table 4 result shows: compared with normal group, it is sagging that reserpine group significantly increases upper eyelid, proves modeling success; Compared with reserpine group, each administration group all in various degree decrease the sagging number (P<0.01, P<0.05) in upper eyelid; Respectively compared with antacid Semen Ziziphi Spinosae group, rotundine group, basic, normal, high dosage group have in various degree decrease the sagging number in upper eyelid (P<0.05).
Experiment brief summary: FUFANG ZAOREN JIAONANG can treat mild depression, desperate type depression, has synergy.
Although above with general explanation, detailed description of the invention and test, the present invention is described in detail, and on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.

Claims (4)

1. the application of FUFANG ZAOREN JIAONANG in the medicine preparing Cure of depression.
2. application according to claim 1, is characterized in that, described depression comprises desperate type depression, manic-depressive illness or mild depression.
3. application according to claim 1, is characterized in that, described depression is desperate type depression or manic-depressive illness.
4. application according to claim 1, is characterized in that, described depression is manic-depressive illness.
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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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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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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