CN108014162A - A kind of application of extractive from leaves of persimmon in treatment is had a sleepless night - Google Patents

A kind of application of extractive from leaves of persimmon in treatment is had a sleepless night Download PDF

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CN108014162A
CN108014162A CN201711334516.XA CN201711334516A CN108014162A CN 108014162 A CN108014162 A CN 108014162A CN 201711334516 A CN201711334516 A CN 201711334516A CN 108014162 A CN108014162 A CN 108014162A
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persimmon
extractive
leaves
insomnia
medicine
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郭海彪
李楚源
王德勤
李淑如
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GUANGZHOU BAIYUNSHAN HEJI HUANGPU CHINESE MEDICINE CO Ltd
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GUANGZHOU BAIYUNSHAN HEJI HUANGPU CHINESE MEDICINE CO Ltd
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Priority to CN202111413241.5A priority Critical patent/CN113995779A/en
Priority to CN201711334516.XA priority patent/CN108014162A/en
Publication of CN108014162A publication Critical patent/CN108014162A/en
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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)
    • A61K36/44—Ebenaceae (Ebony family), e.g. persimmon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/00—Drugs for disorders of the nervous system
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

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Abstract

The present invention relates to a kind of application of extractive from leaves of persimmon in treatment primary insomnia, the especially medicine of difficulty falling asleep type insomnia is prepared.Each dosage group of extractive from leaves of persimmon can dose-dependently increase the mouse quantity that sub-threshold dose yellow Jackets cause sleep, can also dose-dependently shorten the above threshold dropping asleep latency caused by dosage carbrital and extend the above threshold sleep time caused by dosage carbrital.Extractive from leaves of persimmon of the present invention treats primary insomnia, and effective dose is low, and patient compliance and security are good.

Description

A kind of application of extractive from leaves of persimmon in treatment is had a sleepless night
Technical field
The invention belongs to medicine, and in particular to a kind of new medical usage of extractive from leaves of persimmon.
Background technology
Insomnia is one of form of expression of sleep-disorder, typically refers to the generation of sleep and (or) maintains generation obstacle to cause Sleep missing, shows as difficulty falling asleep, Yi Xing, early awakening and difficulty falling asleep, the quality and quantity of sleep cannot meet individual physiology again Need, cause that the daytime is drowsiness, dispirited and a series of neuropsychic symptom.
Insomnia is divided into by modern medicine by the course of disease：Transience insomnia (being less than 1 week), short-term insomnia (1 week to 1 A month) and chronic insomnia (being more than 1 month).Then it is divided into primary insomnia and insomnia secondary by the cause of disease：1. primary insomnia：Root According to Americanism obstacle diagnosis and statistic handbook (DSM-4) primary insomnia diagnostic criteria, primary insomnia refers to " main suit Have difficulty in going to sleep and maintain dyscoimesis, onset at least January；It is sleep disordered to cause worried or society, occupation etc. obstacle；And Exclude caused by the obstacles such as paroxysmal disease, sleep-disorder relevant with breathing, biological rhythm sleep-disorder；Exclusion is pressed down by principal characteristic Caused by the obstacles such as strongly fragrant disease, generalized anxiety disorder；Exclude a kind of body caused by the psychological application of various physical diseases, alcohol or medicine Heart disease "；2. insomnia secondary：It is the insomnia caused by pain, anxiety or depression, therefore also has viewpoint to propose to use " comorbidity Insomnia " replacement " insomnia secondary ".
It is clinical at present to the treatment of insomniac that need to see a doctor still based on medicine.These medicines mainly include gamma-amino Butyric acid A (GABAA) complex excitomotor, melatonin receptors excitomotor, antidepressants, atypical antipsychotics, antihistamine. But the few in number of FDA (Food and Drug Adminstration) (FDA) insomnia idicatio approval are obtained, only including GABAAComplex swashs Dynamic medicine (benzene phenodiazine5 kinds of class, non-benzene phenodiazine4 kinds of class), draw and step ketone (melatonin receptors excitomotor) and low dose of doxepin (resists Depressant drug).Country's treatment insomnia is with GABAABased on complex excitomotor.
To various forms of insomnias, different medicines is selected.Such as the insomnia of difficulty falling asleep type, select sleep inducing effect fast The medicine of speed, wherein most is the hypnotic sedative agent of short-half-life, such as triazolam, midazolam, Oxazepam, Zha Laipu Grand, eszopiclone, zolpidem etc..Easily wake up to night type insomnia, selection can extend NREM and sleep third and fourth phase and shortening The somnifacient of REM sleep time, such as estazolam, Temazepam, nitrazepam, Flurazepam.Early morning awakening is more common in depression Disease patient, while protopathy is treated, effect or long-acting hypnotic sedative agent in can be selected, diazepam, nitrazepam, chlorine nitre west Dissolve.It has been reported that antidepressants, as Mirtazapine for it is shallow sleep it is effective with early awakening patient, but for the patient of difficulty falling asleep It is invalid.
Preferable sedative hypnotic drug should be able to rapid induction sleep, on Sleep architecture without influence, no next day residual action, no Memory function is influenced, apnea inhibitory action, long-time service is without dependence or withrawal symptom.But clinically common treatment at present The medicine of difficulty falling asleep type insomnia, triazolam described above, midazolam, Oxazepam, Zaleplon, eszopiclone, azoles Pyrrole is smooth etc., there is more or less side effect.Wherein, triazolam, midazolam, Oxazepam belong to benzene phenodiazineClass, due to Action target spot poor selectivity, long-time service can cause drug tolerance, dependence and withrawal symptom；It is external at present not as controlling Treat the choice drug of insomnia, particularly the elderly and with respiratory disease patient.Therefore, difficulty falling asleep type insomniac Limitation is compared in medication selection.
In today of social rhythm's quickening, intensified competition, the incidence of insomnia rises, is shown according to the data of WHO, entirely year by year The people that ball has nearly 1/4 is subject to insomnia to perplex, and the insomniac of developing country accounts for the 30%~35% of general population.Insomnia pair Individual and society have a significant impact, and show because the expense and treatment expenditure of traffic accident caused by insomnia increase year by year.Can See that insomnia is both medical problem, and social concern, cause great attention both domestic and external.Therefore, research and develop new The medicine of safer efficient treatment insomnia, will be a lasting research and development focus.
Clinical data shows that Chinese medicine treatment insomnia good effect, adverse reaction is few, is provided for new Insomnia therapy medicine rich Rich resource.
Persimmon leaf (Persimmon leaf) is the fresh or dried leaf of Ebenaceae calamander persimmon, it is used as medicine first recorded in the Ming Dynasty 《The southern regions of the Yunnan Province book on Chinese herbal medicine》" applying swelling sore through red leaves ", and《Book on Chinese herbal medicine is new again》Then record and be used for " controlling cough to spit blood, slake thirst and help produce saliva ".Now it is loaded in 《Chinese Pharmacopoeia》Extractive from leaves of persimmon cure mainly qi depression to blood stasis by main of promoting blood circulation and removing blood stasis, dredging collateral, available for coronary heart disease, cerebral artery congee The cardiovascular and cerebrovascular diseases such as sample sclerosis.With prescription medicine NAOXINQING PIAN made of persimmon leaf ethyl acetate extract in clinical practice To popularization energetically.Find there is one to dizziness, headache, insomnia in the old H-type hypertension observation of curative effect of NAOXINQING PIAN treatment Fixed improvement result (the old H-type hypertension observation of curative effect [J] of NAOXINQING PIAN treatment, Zhou Jing, etc.；The new traditional Chinese medical science, 2014,46 (5)： 38-39).But as it was previously stated, NAOXINQING PIAN observed while hypertension is treated improve insomnia should belong to have pain, Insomnia secondary caused by anxiety or depression.The specific evaluation criteria of insomnia is not disclosed in the research, insomnia improves result and refers to Mark or the particular type of insomnia, lack clinical accurate medication and instruct.
The content of the invention
In view of the deficiencies of the prior art, it is an object of the invention to provide a kind of extractive from leaves of persimmon and its preparation (such as brain The clear piece of the heart, brain heart clearing capsule etc.) treating the new medical usage in having a sleepless night.
In order to realize foregoing invention purpose, present invention employs following technical solution：
A kind of application of extractive from leaves of persimmon in the medicine for preparing treatment primary insomnia.
Preferably, sole active agent of the extractive from leaves of persimmon as the medicine.
Preferably, the primary insomnia is difficulty falling asleep type primary insomnia.
Preferably, the medicine of the treatment primary insomnia is clinically acceptable preparation, including or does not include medicine Acceptable auxiliary material on.
Preferably, the clinically acceptable preparation is oral formulations or non-oral formulation；More preferably oral system Agent.
The oral formulations be selected from powder, normal oral tablet, capsule, soft capsule, pill, pill, micropill preparation, One or more in granule, oral disnitegration tablet and oral quick-dissolving film preparation.
One or more of the non-oral formulation in injection, freeze-dried powder and large capacity transfusion agent.
Application of the present invention, it is mammal in need to grant object, is preferably people in need.
Preferably, the medicine for treating primary insomnia is oral formulations.
Preferably, above-mentioned extractive from leaves of persimmon is prepared via a method which：
Take dry persimmon leaf, add water to cook 2 times, every time 1~2 it is small when, merge decocting liquid, filtration, is concentrated into relative density (60 DEG C) 1.12~1.15, add ethanol to alcohol content up to 80~90%；Stand overnight, leaching supernatant is spare；Sediment with 60~ 70% ethanol washs, and merges cleaning solution, stands overnight, and leaching supernatant, merges with spare supernatant, recycles ethanol, adds suitable Measure water, mix, filtration, filtrate with ethyl acetate extract 4 times and more than, merge ethyl acetate liquid, recovery of acetic acid ethyl ester simultaneously concentrates Into thick paste, low temperature drying, to obtain the final product.
As a preferred embodiment, the medicine of the treatment primary insomnia is NAOXINQING PIAN or brain heart gel resin Capsule.
The medicine of the treatment primary insomnia, when granting people in need by oral way, is extracted with the persimmon leaf Thing meter, dosage can be daily 1.0~10mg/kg weight, be preferably 1.0~5.0mg/kg weight.
By the extractive from leaves of persimmon, pharmaceutically acceptable auxiliary material is added or is added without, according to the side of this area routine Method, you can the medicine of above-mentioned treatment primary insomnia is prepared.
In the specification of the present invention, above-mentioned pharmaceutically acceptable auxiliary material, includes but not limited to：
Diluent：Be selected from starch, dextrin, pregelatinized starch, lactose, microcrystalline cellulose, calcium sulfate, calcium monohydrogen phosphate, Calcium carbonate, magnesia, magnesium carbonate, gel aluminum hydroxide, beta-cyclodextrin, mannitol, sorbierite, methylcellulose, hydroxypropyl first One or more in base cellulose, polyvinylpyrrolidone, sodium cellulose glycolate.
Adhesive：It is fine to be selected from distilled water, ethanol, starch slurry, sodium carboxymethylcellulose, hydroxypropyl cellulose, methyl One or more in dimension element and ethyl cellulose, hydroxypropyl methylcellulose.
Lubricant：One be selected from Stepanol MG, polyethylene glycol, superfine silica gel powder, magnesium stearate, talcum powder Kind is a variety of.
Disintegrant：It is selected from starch (corn, potato), microcrystalline cellulose, alginic acid, sodium alginate, ion exchange Resin, effervesce Acid-Base system, hydroxypropul starch, sodium carboxymethyl starch, Ac-Di-Sol, crospovidone, carboxylic first Base cellulose, calcium carboxymethylcellulose, low-substituted hydroxypropyl cellulose, part alphalysed starch and one kind in microcrystalline cellulose or It is a variety of.
Filmogen：Gelatin, shellac, Arabic gum, agar, starch, dextrin, PVA05-88, PVA17-88 and ethene-vinegar One or more in sour ethylene copolymer (EVA).
Flavouring：The one or more being selected from saccharin sodium, honey element, Aspartame, stevioside and essence class.
Solvent for injection：It is selected from water for injection, sesame oil, tea oil, peanut oil, corn oil, olive oil, cottonseed oil, beans Oil, castor oil and persic oil, ethyl oleate, Ergol, propane diols, polyethylene glycol 400, dimethylacetylamide (DMA), second One or more in alcohol and glycerine.
The present invention is experimentally confirmed, and each dosage group of extractive from leaves of persimmon can dose-dependently increase by penta bar of sub-threshold dose Than the mouse quantity that appropriate sodium causes sleep, and the effect of high dose is suitable with positive control drug alprazolam.Extractive from leaves of persimmon is each Dosage group can also dose-dependently shorten the above threshold dropping asleep latency caused by dosage carbrital and extend above threshold dosage Sleep time caused by carbrital, and the time for falling asleep of high dose group is shorter than positive control drug group, and sleep and continue Time is then slightly shorter than positive control drug alprazolam.Above-mentioned experimental result prompting extractive from leaves of persimmon can shorten time for falling asleep, but It is not extend sleep time excessively, therefore can be used for treating the insomnia of difficulty falling asleep type, while can also be to a certain extent Reduce after effect.In addition, converted according to results of animal, the effective dose of extractive from leaves of persimmon treatment difficulty falling asleep type insomnia The dosage of cardiovascular and cerebrovascular disease is treated less than it.Therefore, it is applied to the extractive from leaves of persimmon of effective dose of the present invention primary Property insomnia (insomnia of difficulty falling asleep type) treatment, patient compliance is good, so as to ensure curative effect.
Embodiment
Illustrate the present invention referring to specific embodiment.It will be appreciated by those skilled in the art that these embodiments are only For illustrating the present invention, it is not limited the scope of the invention in any way.
Experimental method in following embodiments, is conventional method unless otherwise specified.Medicine used in following embodiments Material raw material, reagent material etc., unless otherwise specified, are commercially available products.Wherein, portion of reagent and instrument buy situation such as Under：
Extractive from leaves of persimmon (NXQ)：Chinese medicine Co., Ltd of Guangzhou Hutchison China Trade Holdings, lot number H16P006, preparation method are：
Take dry persimmon leaf, add water to cook 2 times, the 1st time 2 it is small when, the 2nd time 1 it is small when, merging filtrate, filtration, inspissated juice is opposite Density 1.12~1.15 (60 DEG C), adds ethanol to alcohol content up to 85%；Stand overnight, leaching supernatant is spare；Sediment is used 65% ethanol washs 2 times, merges cleaning solution, stands overnight, and leaching supernatant, merges with spare supernatant, recycles ethanol, adds Suitable quantity of water, mixes, and filtration, filtrate is extracted 4 times with ethyl acetate, merges ethyl acetate liquid, and recovery of acetic acid ethyl ester is simultaneously condensed into thick Cream, low temperature drying, to obtain the final product.
Yellow Jackets：(Merck Chemical Engineering Technology Shanghai Co., Ltd.
Alprazolamum：Beijing Yimin Pharmaceutical Co., Ltd.；
Embodiment 1The influence that extractive from leaves of persimmon of the present invention falls asleep yellow Jackets induced mice
1. experimental animal
Healthy kunming mice 60, cleaning grade, female fifty-fifty, the 18~22g of weight of hero.Experimental animal credit number：SCXK (capital) 2014-0004；Mouse adapts to feeding environment one week before experiment, regular grade reality of all Mouse feeders in 21 ± 2 DEG C of temperature Animal house is tested, and follows circadian rhythm.Mouse can freely ingest drinking-water.
2. experimental drug
Extractive from leaves of persimmon (NXQ) is prepared with alprazolam using 0.5% sodium carboxymethylcellulose as solvent, medicine Thing should fully be vortexed mixing before administration.
The preparation of extractive from leaves of persimmon (NXQ)：40mg extractive from leaves of persimmon is dissolved in 0.5% carboxymethyl cellulose of 10ml Sodium, is configured to the storing liquid of 4mg/ml, is needed using preceding by administration, is diluted to corresponding working solution.Such as NXQ high doses 40mg/ Kg, by administered volume 0.1ml/10g, administration concentration is 4mg/ml.
0.25mg alprazolams, are dissolved in 0.5% sodium carboxymethylcellulose of 10ml, are configured to by the preparation of alprazolam The storing liquid of 0.025mg/ml, is needed by administration using preceding, is diluted to corresponding working solution.
3. experiment packet and administration
60 kunming mices are randomly divided into 5 groups, every group 12 by weight, gender：1) blank control group, gavage are given molten Agent, 2) NXQ low dose groups (10mg/kg weight), 3) NXQ middle dose groups (20mg/kg weight), 4) NXQ high dose groups (40mg/ Kg weight), 5) alprazolam (0.25mg/kg weight) group；The equal gastric infusion of each group, is administered by mouse actual weight, to medicine body Product is 0.1ml/10g weight, and blank group gives 0.5% sodium carboxymethyl cellulose solution of same volume.
4. experimental method
The influence that 4.1 pairs of sub-threshold dose yellow Jackets induced mices are fallen asleep
After each group intragastric administration on mice administration 30min, mouse peritoneal injects the yellow Jackets of 28mg/kg weight, is turned over mouse More than normal reflection disappearance 1min is sleep index, records the sleep quantity of each group mouse.
After experiment, medicament elution processing in 1 week is carried out to mouse：Free water and diet, do not give in any form Any medicine.After elution, each group mouse carries out the influence experiment that above threshold dose of sodium pentobarbitone induced mice is fallen asleep.
4.2 pairs of influences that above threshold dose of sodium pentobarbitone induced mice is fallen asleep
After each group intragastric administration on mice administration 30min, the yellow Jackets of 40mg/kg are injected intraperitoneally, observation mice sleep continues Time calculates the time that mouse is repeated from righting reflex loss to righting reflex.
5. statistical analysis
Using SPSS19.0 statistics softwares, measurement data uses mean ± standard deviationRepresent, comparison among groups is adopted Use one-way analysis of variance；Enumeration data comparison among groups uses χ2Examine, P ＜ 0.05 are statistically significant for difference.
6. experimental result
6.1 NAOXINQING PIANs cause sub-threshold dose amobarbital the influence of mouse sleep quantity
The results are shown in Table 1, and compared with blank control group, extractive from leaves of persimmon (NXQ) each dosage can increase to a certain extent Sub-threshold dose yellow Jackets are added to cause the mouse quantity of sleep, its effect is in dose-dependence.In addition, extractive from leaves of persimmon is high Dosage group sleep mouse is 7, and sleep rate reaches 58.3%, acts on that (sleep mouse 8, enters close to positive drug alprazolam Sleep rate 66.7%).
1 extractive from leaves of persimmon of table causes sub-threshold dose amobarbital the influence of mouse sleep quantity and sleep rate
6.2 NAOXINQING PIANs cause above threshold dosage amobarbital the influence of mouse dropping asleep latency and sleep time
The results are shown in Table 2, and compared with blank control group, extractive from leaves of persimmon (NXQ) each dosage can contract to a certain extent When dropping asleep latency and the extension above threshold sleep caused by dosage carbrital caused by short above threshold dosage carbrital continue Between, effect is in dose-dependence；Statistical significance (P ＜ 0.05) of the effect with conspicuousness of the middle and high dosage of wherein NXQ. In addition, the incubation period that extractive from leaves of persimmon high dose inducing mouse is fallen asleep is shorter than positive drug alprazolam, but the length of one's sleep is slightly less than Alprazolam, result prompting extractive from leaves of persimmon can shorten mouse dropping asleep latency and be unlikely to cause the long length of one's sleep.
2 NAOXINQING PIAN of table causes above threshold dosage amobarbital the effect of mouse dropping asleep latency and sleep time
*P ＜ 0.05,**P ＜ 0.01vs. blank control groups
7. conclusion
Each dosage group of extractive from leaves of persimmon can dose-dependently increase sub-threshold dose yellow Jackets and cause the small of sleep Mouse quantity, and the effect of high dose is suitable with positive control drug alprazolam.
Each dosage group of extractive from leaves of persimmon can also dose-dependently shorten the above threshold sleep caused by dosage carbrital Incubation period and the extension above threshold sleep time caused by dosage carbrital, and the time for falling asleep of high dose group is shorter than the positive Comparison medicine group, and sleep time is then slightly shorter than positive control drug alprazolam, illustrates that extractive from leaves of persimmon high dose can be shown Write and shorten mouse dropping asleep latency and be unlikely to cause the long length of one's sleep, the effect that its inducing mouse is fallen asleep is better than A Pu azoles Logical sequence.
The result prompting of the present embodiment：Extractive from leaves of persimmon can be used for treating the insomnia of difficulty falling asleep type, shorten time for falling asleep, But do not extend sleep time excessively, so as to reduce after effect to a certain extent, improve drug safety.
10~40mg/kg of dosage range of the extractive from leaves of persimmon of above-mentioned experiment, according to body surface area coefficient conversion into clinic People is about 1.1~4.4mg/kg weight with dosage range；And《Chinese Pharmacopoeia》Regulation is used to treat coronary heart disease, cerebral arteriosclerosis When, to be 300~600mg/ days oral, be converted to kg body weight doses is extractive from leaves of persimmon usage and dosage：4.3~8.6mg/kg.It is aobvious So, extractive from leaves of persimmon, which is used for the dosage that difficulty falling asleep type of the invention is had a sleepless night, will likely be less than prior art treatment coronary heart disease, brain The dosage of arteriosclerosis.The preparation of same size, then patient's dose of difficulty falling asleep type insomnia can be considerably less than facing at present The conventional usage amount of bed, so as to greatly improve the compliance of medication patient, security, and reduces drug tolerance.
In short, the new medical usage the present invention provides extractive from leaves of persimmon：For treating primary insomnia, especially enter Sleep difficult type insomnia.And importantly, in compared with the prior art it has been reported that to coronary heart disease, cerebral atherosclerosis Deng the treatment of cardiovascular and cerebrovascular disease, extractive from leaves of persimmon can be in the low dose of effect for just playing and shortening time for falling asleep, improving sleep.

Claims (10)

  1. A kind of 1. application of extractive from leaves of persimmon in the medicine for preparing treatment primary insomnia.
  2. 2. application according to claim 1, it is characterised in that sole active of the extractive from leaves of persimmon as the medicine Component.
  3. 3. application according to claim 1 or 2, it is characterised in that the primary insomnia is difficulty falling asleep type primary Insomnia.
  4. 4. application according to claim 1 or 2, it is characterised in that the medicine of the treatment primary insomnia is clinically Acceptable preparation, including or not including pharmaceutically acceptable auxiliary material.
  5. 5. application according to claim 4, it is characterised in that the clinically acceptable preparation for oral formulations or Non-oral formulation；Preferably oral formulations.
  6. 6. application according to claim 5, it is characterised in that the oral formulations are selected from powder, conventional tablet, capsule One or more in agent, soft capsule, pill, pill, micropill preparation, granule, oral disnitegration tablet and oral quick-dissolving film preparation.
  7. 7. application according to claim 5, it is characterised in that the non-oral formulation be selected from injection, freeze-dried powder and One or more in large capacity transfusion agent.
  8. 8. application according to claim 5, it is characterised in that the medicine of the treatment primary insomnia is oral formulations.
  9. 9. application according to any one of claim 1 to 8, it is characterised in that the extractive from leaves of persimmon passes through such as lower section It is prepared by method：
    Take dry persimmon leaf, add water to cook 2 times, every time 1~2 it is small when, merge decocting liquid, filtration, is concentrated into relative density (60 DEG C) 1.12~1.15, add ethanol to alcohol content up to 80~90%；Stand overnight, leaching supernatant is spare；Sediment is with 60~70% Ethanol washs, and merges cleaning solution, stands overnight, and leaching supernatant, merges with spare supernatant, recycles ethanol, adds suitable quantity of water, Mix, filtration, filtrate with ethyl acetate extract 4 times and more than, merge ethyl acetate liquid, recovery of acetic acid ethyl ester is simultaneously condensed into thick Cream, low temperature drying, to obtain the final product.
  10. 10. application according to any one of claim 1 to 9, it is characterised in that the medicine of the treatment primary insomnia For NAOXINQING PIAN or brain heart clearing capsule.
CN201711334516.XA 2017-12-12 2017-12-12 A kind of application of extractive from leaves of persimmon in treatment is had a sleepless night Pending CN108014162A (en)

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CN202111413241.5A CN113995779A (en) 2017-12-12 2017-12-12 Application of persimmon leaf extract in treating insomnia
CN201711334516.XA CN108014162A (en) 2017-12-12 2017-12-12 A kind of application of extractive from leaves of persimmon in treatment is had a sleepless night
AU2018101247A AU2018101247A4 (en) 2017-12-12 2018-08-28 Application of persimmon leaf extract in the preparation of medicines for the treatment of primary insomnia

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