CN1666740A - Application of tetrandrine and Fangchinoline in preparation of medicine for improving sleep and health products - Google Patents
Application of tetrandrine and Fangchinoline in preparation of medicine for improving sleep and health products Download PDFInfo
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- CN1666740A CN1666740A CN 200410006197 CN200410006197A CN1666740A CN 1666740 A CN1666740 A CN 1666740A CN 200410006197 CN200410006197 CN 200410006197 CN 200410006197 A CN200410006197 A CN 200410006197A CN 1666740 A CN1666740 A CN 1666740A
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- tetrandrine
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Abstract
The invention utilizes menispermaceae components including tetrandrine and fangchinoline in the structure of bisbenzylisoquinoline to prepare functional health products and drug which can promote quality of sleeping. It can prepare drug in any form with tetrandrine and fangchinoline as efficient components. And the animal experiment indicates said invention has remarkable impact on the quality of sleeping and applicability on various insomnias.
Description
Technical field
The present invention relates to the new purposes of two kinds of main Dibenzylisoquinolinealkaloids compound powder menispermines (tetrandrine) and fangchinoline (fangchinoline), particularly the application on preparation improvement and treatment sleep disorder medicine.
Background technology
Sleep disorder of the present invention (sleep disorder) mainly is meant insomnias such as the difficulty falling asleep that is caused by a variety of causes, the minimizing of easily waking up, sleep, and is a kind of serious discomfort.The World Sleep Day eve on March 21st, 2002, hygiene department has announced the single sample survey result, among the surveyee, because of have difficulty in going to sleep, easily wake up, wake up too early, the length of one's sleep deficiency, sleep quality bad etc. have that sleep disorder promptly has a sleepless night problem reach 42.5%, the influence that brings therefrom is people over half lassitude, a doze by day, 27.7% people is unhappy, people's active receiving on daytime restriction of 38.9%.Wherein number of women is 1.5 times of male, and 3/4ths is 40～60 years old middle-aged and elderly people.Therefore, solve sleep disorder and become the content that women, old people's psychohygiene must pay attention to.
Insomnia occupies very important ratio in sleep disorder.In the International Classification that nineteen ninety U.S.'s sleep association formulates, the hypotype in the sleep disorder that belongs to dyskoimesis and the spiritual nervous system disease of companion of having a sleepless night.The life events that causes insomnia has: (1) psychological factor: various contradictions in life, the work and the anxiety, depression, anxiety, excitement, the indignation that are caused of difficulty or ponder over too much and all can cause insomnia; (2) with the insomnia of neuropsychiatric disease such as neurosis, affective disorder, schizophrenia etc.Patient neurasthenia often tells the difficulty of falling asleep, insomnia-middle, dreaminess, but show on the EEG(electroencephalography) and do not reduce the length of one's sleep, and the time and the number of times of awakening increase to some extent, and this class patient often has headache, dizziness, symptom such as forgetful, weak, emotional; Existing early awakening of the insomnia multilist of depression or insomnia-middle, the electroencephalography demonstration awakening time obviously prolongs, and whole sleep period shortens, and the REM sleep is in advance; Mania performance fall asleep difficulty even sleeplessness whole night; Schizophrenia can show difficulty falling asleep, insomnia-middle because of influenced by vain hope.(3) physiologic factor: psychentonia, hunger, fatigue, sexual excitation and some diseases all can cause fall asleep difficulty and insomnia-middle as arthritis, Peptic Ulcers, angina pectoris, migraine, asthma, arrhythmia etc.; Along with the rising at age, sleeper effect also can change and cause insomnia; Thalamus pathological changes person can show as the perversion of sleep rhythm, i.e. sleep on daytime, the sleeplessness of regaining consciousness night.(4) medicine factor: drink, drug dependence, drug dependence and withdrawal symptom all can cause insomnia.Common medicine has analeptic, tranquilizer, thyroxine, contraceptive, anti-arrhythmic etc.Insomnia can disappear after the drug withdrawal.(5) bad environment and custom: bad environment or bad habit all can influence sleep for most people.As the strong and weak heat of noise, light is cold the people is had a sleepless night, satiety or hungry, strenuous exercise and work and rest and irregularly all can influence sleep just before going to bed.
Radix stephaniae tetrandrae subtracts with fangchinoline and belongs to bisbenzylisoquinoline alkaloid, be natural calcium ion antagonist, be Menispermaceae Radix stephaniae tetrandrae (Stephania tetrandra), hair vane rings rattan (Cyclea barbata (Wall.) Miers), Cyclea densifiora (Yamamoto) Y. C Tang et. S. L. L. (Cyclea densiflora (Yamamoto) Y.C.Tang et S.L.Lo[C.gracillima Diels]), Herba Hypserpae Nitidae (Hypserpa nitida Miers), Radix Stephaniae Cepharanthae (Stepahania cepharanthaHayata[S.tetrandra S.Moor var.glabra Maxim.; S.disciflora Hand.Mazz]), Hainan Radix Stephaniae Epigaeae (Stephaniae Hainanensis), the main chemical compositions of Caulis menispermi plants such as (Menispermum dauricum DC).
Tetrandrine has pharmacological actions widely such as antiinflammatory, analgesia, rheumatism, antitumor, anti-pneumosilicosis, blood pressure lowering, anti-arrhythmia.Be used for the treatment of in one's early years rheumatalgia, arthralgia, neuralgia; Also be applicable to the treatment of simple silicosis I, II, III phase and each phase anthracosilicosis; Merge with the low dose radiation, be used for the treatment of pulmonary carcinoma.Recent study finds that tetrandrine energy reversing tumor chemotherapy multidrug resistance (MDR) strengthens the short lethal effect of cancer therapy drug to tumor cell, improves the chemotherapy of tumors effect; Liver cirrhosis patient is had the portal vein of reduction blood pressure, anti-liver knot fibrosis and improves liver function, make fibrous tissue minimizing in the liver.Now, tetrandrine not only has general formulations such as oral tablet, injection, aerosol, soft capsule, and simultaneously, (drug delivery system, research DDS) also constantly occurs to be made into novel drug-supplying systems such as liposome, microsphere.Clinically mainly as antirheumatic and anticancer synergia medicine.Be used for rheumatism, arthralgia, neuralgia; Be used for pulmonary carcinoma with low dose radiation merging, also be applicable to simple silicon I, II, III phase and each phase anthracosilicosis.Yet, to the improvement of tetrandrine and derivant fangchinoline thereof or treatment sleep disorder, prolong the length of one's sleep, make the pharmacological action and the clinical practice thereof that are easy to aspects such as falling asleep, do not see any research report so far as yet.
Can improve sleep function in order from Chinese medicine, natural drug, to seek, and be used for the treatment of the insomnia's that a variety of causes causes chemical compound, multiple native compound is screened, found that, chemical compound with Bisbenzylisoquinolincompounds structure, tetrandrine and fangchinoline can produce the obvious synergistic effect with pentobarbital sodium in the whole animal experiment, prolong the length of one's sleep.
Summary of the invention
The object of the present invention is to provide tetrandrine and derivant fangchinoline thereof new indication and the purposes in clinical practice, i.e. application on improvement or the Cure for insomnia symptom.
Described tetrandrine and fangchinoline all have Bisbenzylisoquinolincompounds structure (Bisbenzylisoquinoline).
Tetrandrine or fangchinoline can be used for preparing treatment and improve the insomnia's that a variety of causes causes health product or medicine.
Further specify the present invention below in conjunction with accompanying drawing and concrete experiment.
Description of drawings
What Fig. 1 showed is tetrandrine and fangchinoline structure.
Fig. 2 shows is tetrandrine to the influence of the length of one's sleep of dosage pentobarbital sodium induced mice above threshold.
Fig. 3 shows is fangchinoline to the influence of the length of one's sleep of dosage pentobarbital sodium induced mice above threshold.
Fig. 4 shows is tetrandrine to the preclinical influence of sleeping of dosage pentobarbital sodium induced mice above threshold
Fig. 5 shows is fangchinoline to the preclinical influence of sleeping of dosage pentobarbital sodium induced mice above threshold
The specific embodiment
Experiment one, tetrandrine and fangchinoline are to the dosage pentobarbital sodium induced mice length of one's sleep and the preclinical influence of sleeping above threshold.
Get 20.0 ± 2.0g male ICR mouse by the body weight random packet, matched group is irritated stomach 0.2ml water/10g, all the other each group irritates respectively that stomach is stable, tetrandrine and fangchinoline, behind the administration 1h, lumbar injection is the 40mg/kg pentobarbital sodium of dosage above threshold, with lumbar injection pentobarbital sodium to mice righting reflex loss is sleep incubation period, is the length of one's sleep with mice righting reflex loss to righting reflex time of occurrence.The sleep incubation period and the length of one's sleep of mice respectively organized in record.Experimental result such as table one, Fig. 2, Fig. 3, Fig. 4 and shown in Figure 5, tetrandrine 15,30,60mg/kg and fangchinoline 30,60mg/kg gastric infusion, all obviously prolong the dosage pentobarbital sodium induced mice length of one's sleep (P＜0.05) above threshold, and obviously shorten dropping asleep latency.Show that tetrandrine and fangchinoline all can strengthen the syngignoscism of dosage pentobarbital sodium above threshold.
Table one.Tetrandrine and fangchinoline are to (the mean ± SE) of the dosage pentobarbital sodium induced mice length of one's sleep and the preclinical influence of sleeping above threshold.
| Group | Dosage (mg/kg) | ????N | Dropping asleep latency (branch) | The length of one's sleep (branch) |
| Matched group | ????20 | ????7.2±0.3 | ????10.7±1.5 | |
| Stable group | ????2 | ????15 | ????5.1±0.5 *** | ????53.7±7.4 *** |
| The tetrandrine group | ????60 | ????15 | ????5.3±0.7 *** | ????27.1±1.9 *** |
| ????30 | ????15 | ????5.8±0.4 * | ????23.4±1.9 *** | |
| ????15 | ????15 | ????6.0±0.4 * | ????22.6±1.7 ** | |
| The fangchinoline group | ????60 | ????15 | ????4.3±0.4 *** | ????21.1±2.8 * |
| ????30 | ????15 | ????5.2±0.5 ** | ????20.6±2.9 * | |
| ????15 | ????15 | ????7.1±0.8 | ????17.8±3.1 * |
Annotate:
*,
*With
* *Expression is compared P＜0.05,0.01,0.001. with matched group
Experiment two, tetrandrine and fangchinoline are to the influence of the sleeping rate of sub-threshold dose pentobarbital sodium intraperitoneal injection of mice.
Get 20.0 ± 2.0g male ICR mouse by the body weight random packet, matched group is irritated stomach 0.2ml water/10g, all the other each group irritates respectively that stomach is stable, tetrandrine and fangchinoline, the 30mg/kg pentobarbital sodium of 1h lumbar injection sub-threshold dose after the administration, in injection pentobarbital sodium 30min, the mice righting reflex loss is sleeping judge index.Each group of record go into the glirid number.Experimental result as shown in Table 2, tetrandrine 15,30,60mg/kg and fangchinoline 30,60mg/kg gastric infusion, all obviously increase the sleeping quantity (P＜0.05) of sub-threshold dose pentobarbital sodium induced mice, and each group is gone into and to be compared by (table three) between length of one's sleep of glirid, and all obviously prolong (P＜0.05) than the sleeping mice of blank group the length of one's sleep of the sleeping mice of tetrandrine and fangchinoline administration group.Show that tetrandrine and fangchinoline all have collaborative syngignoscism with the sub-threshold dose pentobarbital sodium.
Table two.Tetrandrine and fangchinoline and sub-threshold dose pentobarbital sodium are to the synergism of the sleeping rate of mice
| Group | Dosage (mg/kg) | Go into glirid number/total Mus number | Sleeping rate (%) |
| Matched group | ?7/30 | ?23.3 | |
| |
2 | ?13/14 | ?92.9 *** |
| The |
60 | ?25/30 | ?83.3 *** |
| 30 | ?16/21 | ?76.2 *** | |
| 15 | ?9/16 | ?56.25 * | |
| The |
60 | ?9/15 | ?60.0 ** |
| 30 | ?8/15 | ?53.3 * | |
| 15 | ?2/15 | ?13.3 |
Annotate:
*,
*With
* *Expression is compared P＜0.05,0.01,0.001. with matched group
Table three.Tetrandrine and fangchinoline are to sub-threshold dose pentobarbital sodium induced mice dropping asleep latency and the influence of the length of one's sleep (mean ± SE).
| Group | Dosage (mg/kg) | ????N | Dropping asleep latency (branch) | The length of one's sleep (branch) |
| Matched group | ????20 | ????13.6±1.5 | ????11.8±0.8 | |
| Stable group | ????2 | ????15 | ????6.2±1.0 *** | ????19.0±2.3 *** |
| The tetrandrine group | ????60 | ????15 | ????7.4±0.4 *** | ????18.5±1.4 *** |
| ????30 | ????15 | ????7.4±1.4 * | ????17.3±3.7 *** | |
| ????15 | ????15 | ????7.0±1.4 * | ????17.8±3.2 ** | |
| The fangchinoline group | ????60 | ????15 | ????5.9±0.7 *** | ????17.3±2.2 * |
| ????30 | ????15 | ????5.7±1.1 ** | ????14.7±2.5 | |
| ????15 | ????15 | ????7.0±2.0 * | ????14.5±3.5 |
Annotate: all derive from the length of one's sleep and gone into glirid, average (mean) is organized into the glirid number for removing each the length of one's sleep;
*,
*With
* *Expression is compared P＜0.05,0.01,0.001 with matched group.
Claims (4)
1. the purposes of menispermaceous plants active component tetrandrine and fangchinoline is characterized in that being used to prepare health product or the medicine that the treatment a variety of causes causes the insomnia and improves sleep.
2. as claim 1 described menispermaceous plants, it is characterized in that comprising menispermaceous plants Radix stephaniae tetrandrae (Stephania tetrandra), hair vane rings rattan (Cyclea barbata (Wall.) Miers), Cyclea densifiora (Yamamoto) Y. C Tang et. S. L. L. (Cyclea densiflora (Yamamoto) Y.C.Tang et S.L.Lo[C.gracillima Diels]), Herba Hypserpae Nitidae (Hypserpa nitida Miers), Radix Stephaniae Cepharanthae (Stepahania cepharantha Hayata[S.tetrandra S.Moor var.glabra Maxim.; S.discifloraHand.Mazz]), Hainan Radix Stephaniae Epigaeae (Stephaniae Hainanensis), Caulis menispermi (Menispermum dauricumDC).
3. as claim 1 described active component, it is characterized in that tetrandrine and fangchinoline all have the Bisbenzylisoquinolincompounds structure.
4. as claim 1 described health product or medicine, it is characterized in that to add various calmness, hypnotic drug or excipient and make clinical acceptable forms.
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| CNB2004100061976A CN100363002C (en) | 2004-03-08 | 2004-03-08 | Application of tetrandrine and Fangchinoline in preparation of medicine for improving sleep and health products |
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| CNB2004100061976A CN100363002C (en) | 2004-03-08 | 2004-03-08 | Application of tetrandrine and Fangchinoline in preparation of medicine for improving sleep and health products |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102274227A (en) * | 2011-06-23 | 2011-12-14 | 天津中医药大学 | Application of tetrandrine in preparation of drug for prevention and/or treatment of depression |
| CN102552266A (en) * | 2011-03-18 | 2012-07-11 | 北京大学 | Application of bisbenzylisoquinoline compound or pharmaceutically acceptable salt thereof in preparing medicine or healthcare product for improving sleep |
| CN103356620A (en) * | 2012-04-06 | 2013-10-23 | 北京大学 | Novel use of bisbenzylisoquinoline compounds or pharmaceutically acceptable salts thereof in treating or improving depressive symptom |
-
2004
- 2004-03-08 CN CNB2004100061976A patent/CN100363002C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552266A (en) * | 2011-03-18 | 2012-07-11 | 北京大学 | Application of bisbenzylisoquinoline compound or pharmaceutically acceptable salt thereof in preparing medicine or healthcare product for improving sleep |
| CN102274227A (en) * | 2011-06-23 | 2011-12-14 | 天津中医药大学 | Application of tetrandrine in preparation of drug for prevention and/or treatment of depression |
| CN102274227B (en) * | 2011-06-23 | 2013-07-03 | 天津中医药大学 | Application of tetrandrine in preparation of drug for prevention and/or treatment of depression |
| CN103356620A (en) * | 2012-04-06 | 2013-10-23 | 北京大学 | Novel use of bisbenzylisoquinoline compounds or pharmaceutically acceptable salts thereof in treating or improving depressive symptom |
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| CN100363002C (en) | 2008-01-23 |
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Granted publication date: 20080123 Termination date: 20130308 |