CN101077357A - Application for extration of glossy ganoderma in preparing medicine and health products for treating and improving depression symptoms a variety of causes resulting sleep disorder - Google Patents
Application for extration of glossy ganoderma in preparing medicine and health products for treating and improving depression symptoms a variety of causes resulting sleep disorder Download PDFInfo
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- CN101077357A CN101077357A CN 200610081515 CN200610081515A CN101077357A CN 101077357 A CN101077357 A CN 101077357A CN 200610081515 CN200610081515 CN 200610081515 CN 200610081515 A CN200610081515 A CN 200610081515A CN 101077357 A CN101077357 A CN 101077357A
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Abstract
The present invention provides one kind of glossy ganoderma extract for preventing and treating depression and sleep disorder of different causes. The glossy ganoderma extract contains glossy ganoderma polysaccharides, nucleosides, furans, sterols, alkaloids, amino acids and tritrepenes, as well as inorganic ions, organogermanium, etc. It may be mixed with various kinds of depression resisting, tranquilizing and hypnotic medicine and excipient to prepare medicine and health product for preventing and treating depression and sleep disorder of different causes.
Description
Technical field
Depression is clinical common mood disorders disease, sickness rate height, serious harm patient physical and mental health.Along with social development, rhythm of life is accelerated, the employment competition aggravation, and sickness rate can increase year by year.WHO estimates that the whole world has surpassed 300,000,000 patients, at present, occupies the 4th of disease.It is predicted, might be upgraded to the 2nd to the year two thousand twenty.The suicidal tendency of depression is very serious, homicide rate about 15%.The pathogeny complexity of depression, clinical disease is various.The main feature of depressive state is a depressive mood.Be embodied in sorrow, pessimism, despair.And the pleasant sensation forfeiture also is one of depressed patient common sympton.Body or biology symptom mainly show as symptom biology such as loss of appetite, sleeping eyes obstacle, sexual disorder and mental state day and night fluctuation.
About clinically 90% above mood disorders patient can occur sleep disordered in a certain period, and sleep disordered be depression the earliest with one of modal symptom.From the treatment angle, sleep disorder is one of the most painful incident of patients with depression.Many patients usually often tell and lie awake all night that spirit is very wan and sallow, and sense overwhelmed with sorrow is arranged more.The improvement of patients with depression sleep quality has important effect to alleviate depression symptom, promotion rehabilitation.Discover that the state of an illness is heavy more, sleep disorder is obvious more, and the clinical treatment difficulty is also big more.The state of an illness is light more, and sleep disorder is light more, and clinical therapeutic efficacy is also good more, and rehabilitation is very fast.Research finds that simultaneously sleep disorder is the key factor that increases the weight of the depression state of an illness, is one of major obstacle that influence the patients with depression rehabilitation, and sleep disorder also is to cause one of depressed factor that takes place, and both are reciprocal causation often, the formation vicious cycle.Studies show that the more non-insomnia crowd's of insomnia crowd rate of depression is high 4 times.And depression insomnia group suicide incidence rate is apparently higher than non-insomnia group, and the suicide risk degree of insomnia group is also apparently higher than non-insomnia group.The prompting clinician will give good psychotherapy and appropriate Drug therapy to the sleep disorder of patients with depression, otherwise influences rehabilitation of patients and prognosis.Earlier the sleep disorder reason is analyzed and appropriate treatment, can be reduced the sickness rate of depression, patient's depression tendency is eliminated in bud.
The research of relevant patients with depression sleep behavior and sleep physiology obstacle is more, finds that the Sleep architecture of patients with depression and sleeping process all change to some extent.The suggestion that reaches unanimity at present mainly contains: (1) sleep seriality is impaired; (2) the rapid eye movement sleep shortens (REMs) incubation period, all increases to some extent of quantity, intensity and density of REMs; (3) deep sleep reduces.Most scholars think that wherein some biological property of depression sleep disorder has been represented in the change of REMs index.Longitudinal study shows that when depressive symptom was alleviated, sleep incubation period and sleep persistence returned within normal range.But the deep sleep minimizing still can continue, and this unusual continuing usually is the tendency that in the future recurs.Pointing out sleep disordered may be a quality feature of depression.It occurs prior to paralepsy, still continues later to exist at paralepsy.Former study report and the early-stage Study result of this research department show that this problem is intended the chronic Unpredictability stress rats depression model of employing, behavior and the sleep disordered phenomenon very close with patients with depression can occur.
Ganoderma (Ganoderma lucidum) is the Polyporaceae plant, and chinese tradition medical science is considered as strengthening by means of tonics for a long time always, consolidates the precious Chinese herbal medicine of setting upright.According to the argumentation in Shennong's Herbal and the Compendium of Material Medica, Ganoderma has functions such as " the beneficial motive ", " going into the heart being responsible for production of blood ", " protecting refreshing ", " beneficial vital essence ", says that promptly Ganoderma has replenishing QI and blood, the function of tranquilizing mind.Ancient Chinese medicine doctor as good medicine, cures mainly diseases such as asthenia, insomnia, spiritlessness and weakness with it.We are in previous research work, and discovery Ganoderma extract significant prolongation is the pentobarbital sodium length of one's sleep of dosage above threshold, shortens dropping asleep latency.In view of the above, we think that Ganoderma extract has good syngignoscism, therefore further studied Ganoderma extract, effect on chronic Unpredictability stress depression animal model has found that Ganoderma extract has treatment and improves depressive symptom and improve the effect of the sleep disorder that a variety of causes causes.
Background technology
Related Ganoderma extract mainly contains polysaccharide, ucleosides, furans, sterols, alkaloids, aminoacid protein class, triterpenes, also has inorganic ions, organic germanium etc. among the present invention.Pharmacological research has been deep into cell, molecular level, and has tentatively inquired into the mechanism of Ganoderma strengthening the body resistance.Wherein the immunologic enhancement of ganoderan is clearer and more definite.And the sleep disordered improvement effect research that the antidepressant effect of Ganoderma extract and various factors cause is not appeared in the newspapers as yet.Symptoms such as the prompting of our result of study, Ganoderma extract be to the depression behavior, i.e. despair, pleasant sensation forfeiture and multiple Unpredictability stress be caused has sleep disorderedly all demonstrated inhibition and improvement effect.And this effect belongs to discovery first.Comprehensive above the analysis, we study with the Ganoderma extract that improves sleep disorder having antidepressant effect, and have finished the present invention.
The Ganoderma extract preparation method that arrives involved in the present invention:
Ganoderma extract: with Polyporaceae Ganoderma fungus Ganoderma (Ganoderma lucidum (Leyss. Ex Fr.) Karst.) Ganoderma lucidum (Leyss.ex Fr.) Karst. and Ganoderma Ganoderma.sinense Zhao, Xu et Zhang is a raw material, take water extraction-alcohol precipitation legal system to get, its yield is about 10%.Identify that with analytical methods such as sulfuric acid-phynol method, acrylamide disc electrophoresis purity of polysaccharide is about 26.5%.Contained polysaccharide (polysacchride) comprises GL-1,2,3,4, ganoderan (ganoderan) A, B, C, and BN3A, BN3B, BN3C, Ganoderma lucidum (Leyss. Ex Fr.) Karst. polysaccharide GLA, GLB, GLC etc.Protein content is about 2.52%; Identify through chemical-agent technique, nucleoside, furan, sterol, alkaloid, albumen, triterpene and inorganic ions reaction can take place.
Summary of the invention
The present invention relates to,
1. one kind is used for the treatment of and improves depressive symptom and improve the Ganoderma extract of the sleep disorder that a variety of causes causes.
2. use separately in this extract or add various antidepressants, calmness, hypnotic drug, adjuvant therapy medicaments or excipient to can be made into clinical acceptable forms, be used for the treatment of and improve the sleep disorder that depressive symptom and a variety of causes cause.
The specific embodiment
Following experimental example or embodiment are used to further specify the present invention.
Experimental example one.Ganoderma extract to chronic Unpredictability stress the mice pentobarbital sodium influence of the inductive length of one's sleep.
Test method:
The foundation of chronic Unpredictability Stress model and experimental technique: stimulate content to comprise: (10 ℃ of forced swimmings, 6min), the folder tail is (apart from root of the tail 1cm place, 1min), taboo water (24h), fasting (24h), lonely foster (24h), outstanding tail (1h), braking (2h), high speed level are shaken (120 times/min, 1h), vola electric shock 45min (average 1mA, time-histories 1s, 1 time/1min).The chronic stress time-histories amounts to 21 days, and once a day, a kind of stimulation mode of picked at random stimulates.Time: between the morning 9:00～afternoon 2:00.Every day in stress before 60min, each treated animal respectively by body weight give Ganoderma extract (240mg/kg, p.o.), distilled water (blank group and stress matched group) or imipramine (14mg/kg, i.p.).Carried out the experiment of behavioristics and analyses of sleep phase on the 22nd day.
As shown in table 1, stress matched group than blank group, pentobarbital sodium (45mg/kg, i.p.) inductive length of one's sleep, significance reduced (P＜0.05); Stress+Ganoderma extract 240mg/kg group (P＜0.05), stress+imipramine 14mg/kg group (P＜0.005) with stress matched group relatively, pentobarbital sodium all has significance to increase the inductive length of one's sleep.
Table 1.Ganoderma extract to chronic Unpredictability stress the mice pentobarbital sodium the inductive length of one's sleep influence (mean ± S.E.M, n=10).
| Group | The length of one's sleep (min) |
| Blank stress control group stress+Ganodenna Lucidum P.E 60mg/kg 120mg/kg 240mg/kg stress+imipramine 14mg/kg | 56.36±4.59 43.80±2.97* 45.64±4.60 46.82±4.95 54.18±2.78# 60.63±4.28# |
*Compare with the blank group P＜0.05; #P＜0.05 with stress matched group relatively.
Experimental example two.Ganoderma extract is the same to the foundation and the experimental technique of the chronic Unpredictability Stress model of influence of chronic Unpredictability stress rats non-swimming time.
The motionless state that rat occurs in the forced swimming model has reflected the desperate behavior of animal, but the depressive state of simulating human.Chronic stress is tested and was carried out the forced swimming experiment on the 22nd day, and experimental result sees Table 2.Stress group and normal control group relatively, the rats'swimming dead time significantly increases (P＜0.01), illustrates that depression model sets up.Ganoderma extract (240mg/kg, p.o.) and fluoxetine (15mg/kg, p.o.) can significantly reduce (P＜0.001) stress be after 21 days the non-swimming time of rat.Prompting, Ganoderma extract can improve the desperate behavior of depression.
Table 2.Ganoderma extract to the influence of chronic Unpredictability stress rats non-swimming time (mean ± S.E.M., n=10).
| Group | Non-swimming time (min) |
| Blank stress control group stress+Ganodenna Lucidum P.E 120mg/kg 240mg/kg stress+Prozac 15mg/kg | 37.75±11.74 107.50±15.49 ** 44.60±4.66## 41.33±8.11## 12.67±5.60## |
*Compare with the blank group P＜0.01; ##P＜0.01 with stress matched group relatively.
Experimental example three.Ganoderma extract is the same to the foundation and the experimental technique of the chronic Unpredictability Stress model of influence of the chronic Unpredictability stress rats sucrose solution amount of drinking.
The minimizing of the sucrose solution amount of drinking is the investigation index of chronic Unpredictability stress rats pleasant sensation forfeiture degree.In 21 days chronic stress processes, respectively at the 1st, 8,15 and 22 day, after stress finishing every day, prohibit water, fasting, give sucrose water and light water behind the 20h again, measure the volume of rat institute drinking water through 1h.Because of amount of drinking water and body weight positive correlation, so calculate reliable relative amount of drinking water, promptly amount of drinking water is investigated with the ratio of body weight.The result shows (seeing Table 3), chronic stress the 15th day and the 22nd day, the chronic stress rat model sucrose solution amount of drinking relatively obviously reduces, and Ganoderma extract group and fluoxetine group were compared with the Stress model group at the 15th and 22 day, had promptly shown tangible increase (P＜0.05).Prompting, Ganoderma extract can suppress the formation of pleasant sensation forfeiture symptom due to the chronic stress.
Table 3.Ganoderma extract to the influence of the chronic Unpredictability stress rats sucrose solution amount of drinking (mean ± S.E.M., n=10).
| The amount of drinking/body weight (ml/kg) | The 1st day | The 8th day | The 15th day | The 22nd day |
| Blank group blank+GLE240 stress contrast stress+fluoxetine 15 stress+GLE 240 | 38.62±3.32 40.71±2.43 39.84±3.25 39.94±3.53 38.14±2.54 | 36.50±2.41 38.62±3.52 35.88±1.53 38.52±5.01 36.85±1.31 | 39.15±3.24 36.89±2.55 25.45±2.11* 36.41±4.36# 32.65±3.61# | 36.10±4.73 35.22±2.32 22.09±2.51* 34.83±2.13# 33.10±2.15# |
GLE 240: Ganoderma extract 240mg/kg; Fluoxetine 15: fluoxetine 15mg/kg.
*Compare with the blank group amount of drinking on the same day P＜0.05; #P＜0.05 with stress matched group on the same day the amount of drinking relatively.
Experimental example four.The influence of the sleep composition of the chronic Unpredictability stress rats of Ganoderma extract
The foundation and the experimental technique of chronic Unpredictability Stress model are the same.
Rat sleep cerebral electricity record and analytical method: choose body weight 200～220g SD male rat, brain electricity and electromyographic electrode are installed in operation.Intramuscular injection 100,000 unit penicillins were in case postoperative wound infection after operation was finished.After 7 days convalescent period, rat carries out chronic Unpredictability stress stimulation every day, and method is the same, and totally 21 days, various stimulation contents are interspersed at random carried out, and simultaneously, 60min (8:00a.m) oral administration gavage Ganoderma extract once before stimulating every day.Each organizes rat stimulated preceding 2 days at chronic stress, stress the 1st, 8,15,22 days, and every day, 9:00a.m.～16:00p.m. measured sleep cerebral electricity (EEG) and the myoelectricity (EMG) of rat respectively.Eeg recording same day gives Ganoderma extract 240mg/kg or distilled water, behind the 60min, rat and mouse cage is put into quiet screened room together.Brain electricity and myoelectricity are connected on the polygraph (BIOPAC MP150).Be recorded in EEG and EMG under the rat free movement state.Adopt sleep analysis software SleepSign, to the sleep cerebral electricity of record, the myoelectricity data are analyzed.
By table 4 as seen, stress the 15th and 22 day, stress group rat sleep total time and blank group be no significant difference relatively, but the frequency of rapid eye movement sleep (REM) time, appearance obviously increases, and REM sleep incubation period (sleeping back is to the time that the REM sleep occurs for the first time) and deep sleep (SWS) obviously shorten.Prompting, through chronic Unpredictability stress after, began promptly to occur the sleep disordered phenomenon similar on the 15th day with patients with depression.And chronic stress is given and Ganoderma extract simultaneously, can increase the deep sleep time significantly, and makes REM length of one's sleep, incubation period and frequency all trend towards normally (P＜0.05), and the persistence of sleep is kept.The result shows, Ganoderma extract can obviously improve chronic Unpredictability stress due to sleep disorder.
The influence of phase when table 4 Ganoderma extract is slept to chronic Unpredictability stress rats (means ± S.E.M., n=8).
| Time (min) | The REM sleep | REM incubation period | The SWS sleep | Total sleep |
| The 15th day blank control group stress group stress+the 22nd day blank control group stress group of Ganodenna Lucidum P.E 240 stress+Ganodenna Lucidum P.E 240 | 19.73±7.55 59.1±6.52 * 48.54±5.97 31.12±3.39 66.79±9.14 * 40.06±7.75# | 26.22±3.86 14.45±1.14 * 11.56±3.23 48.05±16.16 7.21±2.59 * 27.82±6.51# | 32.74±6.74 17.24±7.16 * 62.70±11.05# 40.46±8.25 26.57±7.69 * 82.99±13.77# | 166.73±8.80 221.25±17.76 * 222.28±18.93 201.44±22.24 235.29±9.10 250.32±9.11 |
Ganoderma extract 240:240mg/kg;
*Compare with the blank group P＜0.05; Compare with stress group #P＜0.05.
Claims (3)
1, a kind of Ganoderma extract that is used for the treatment of and improves depressive symptom is characterized in that this extract comprises ganoderan class, ucleosides, furans, sterols, alkaloids, aminoacid protein class, triterpenes, inorganic ions, organic germanium etc.
2, extract according to claim 1 can be used for improving the sleep disorder that a variety of causes causes.
3, extract according to claim 1 is characterized in that, adds various antidepressants, calmness, hypnotic drug or excipient and can be made into clinical acceptable forms.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2011077063A1 (en) * | 2009-12-24 | 2011-06-30 | Roquette Freres | Use of polysaccharides for treating stress and anxiety |
| CN105012356A (en) * | 2014-04-30 | 2015-11-04 | 北京冠瑞金生物科技有限公司 | Application of ganoderic acid A to anti-depression |
| CN110183522A (en) * | 2019-05-29 | 2019-08-30 | 北京市农林科学院 | A kind of glycopeptide and the preparation method and application thereof with antidepression function |
| CN112618552A (en) * | 2020-12-30 | 2021-04-09 | 首都医科大学 | Application of ganoderic acid A or derivative of ganoderic acid A in preparation of medicine for treating autism |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011077063A1 (en) * | 2009-12-24 | 2011-06-30 | Roquette Freres | Use of polysaccharides for treating stress and anxiety |
| FR2954700A1 (en) * | 2009-12-24 | 2011-07-01 | Roquette Freres | USE OF POLYSACCHARIDES IN THE TREATMENT OF STRESS AND ANXIETY |
| US8871740B2 (en) | 2009-12-24 | 2014-10-28 | Roquette Freres | Use of polysaccharides for treating stress and anxiety |
| CN105012356A (en) * | 2014-04-30 | 2015-11-04 | 北京冠瑞金生物科技有限公司 | Application of ganoderic acid A to anti-depression |
| WO2015165382A1 (en) * | 2014-04-30 | 2015-11-05 | 北京冠瑞金生物科技有限公司 | Use of ganoderic acid a for anti-depression |
| CN105012356B (en) * | 2014-04-30 | 2018-10-16 | 北京冠瑞金生物科技有限公司 | Purposes of the ganoderic acid A in depression |
| CN110183522A (en) * | 2019-05-29 | 2019-08-30 | 北京市农林科学院 | A kind of glycopeptide and the preparation method and application thereof with antidepression function |
| CN112618552A (en) * | 2020-12-30 | 2021-04-09 | 首都医科大学 | Application of ganoderic acid A or derivative of ganoderic acid A in preparation of medicine for treating autism |
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