CN104398601B - A kind of pharmaceutical composition treating insomnia and preparation method thereof - Google Patents

A kind of pharmaceutical composition treating insomnia and preparation method thereof Download PDF

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Publication number
CN104398601B
CN104398601B CN201410685210.9A CN201410685210A CN104398601B CN 104398601 B CN104398601 B CN 104398601B CN 201410685210 A CN201410685210 A CN 201410685210A CN 104398601 B CN104398601 B CN 104398601B
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extract
reflux
herba calthae
preparation
ether
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CN104398601A (en
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张寿涛
马慧
林绪涛
孙慧莉
尚义美
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Secret Biography (Beijing) Technology Co., Ltd.
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Binzhou Medical University Hospital
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/71Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/35Extraction with lipophilic solvents, e.g. Hexane or petrol ether
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
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  • Microbiology (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

The invention discloses a kind of pharmaceutical composition treating insomnia and preparation method, this medicine by Herba Calthae extract and pharmaceutically can adjuvant be prepared from, the described ether extract that Herba Calthae extract is Herba Calthae;Preparation method is: by Herba Calthae through petroleum ether reflux, extract, filters, and filtrate discards, and gained filtering residue extracts through aether backflow, to obtain final product.The present invention can not only shorten time for falling asleep, i.e. shortens the sleep derivation phase, and can extend the length of one's sleep, and deepens Depth of sleep.

Description

A kind of pharmaceutical composition treating insomnia and preparation method thereof
Technical field
The invention belongs to active components of plants extractive technique field, in particular to a kind of drug regimen treating insomnia Thing and preparation method thereof.
Background technology
Insomnia is one of clinical modal symptom, be sleep originate and maintain generation obstacle, sleep quality can not meet Human Physiology needs, thus affects normal activity on daytime, occurs the one of the symptoms such as fatigue, aprosexia, bradykinesia Plant sleep disorder syndrome.Modern life rhythm is increasingly faster, and many people have the immense pressure from various aspects, make Obtain ortho sleep can not be guaranteed, have groups of people cannot fall asleep because pressure is huge.Often insomnia causes attention not collect In, understandability declines, the learning efficiency reduces, hypomnesis, thus affect the duty of people, have a sleepless night for a long time Also can reduce the immunity of body, cause endocrine disturbance, easily induce and increase the weight of gastrointestinal disease, infectious disease, the heart Cerebrovascular disease etc..For alleviating these pressure, the Benzodiazepines such as insomniac often relies on hypnotic drug and falls asleep, diazepam Class sedative hypnotic, but these medicines help fall asleep while also bring a lot of side effect, as additive, drug resistance, Chronic toxicity.And, continuous application easily produces giddy, the untoward reaction such as drowsiness, weak.There are some researches show many Chinese herbal medicine has good sedative-hypnotic effect, and untoward reaction is less, without additive, therefore, seeks from natural plants Look for new sedative hypnotic drug to seem to be even more important.
Herba Calthae is the herb of cohosh kincup, belongs to perennial herb, high 40~60 centimetres;Rhizome is sturdy, Crawl.Stem purple, hollow, normal branch;Basal leaf oval or heart, diameter 5~12 centimetres, edge tool rough sawn tooth, Base portion is the most heart-shaped, and two sides is without hair;Petiole length 6~15 centimetres, purple green;Stem leaf and basal leaf similar shape, have stipule, The leaf tool handle of bottom, upper leaf stockless.Uniparous cyme is born in stem or branch top, brightly yellowish color, diameter 1.6~3.2 Centimetre;Sepal 5, petal-shaped, ovum shape is oval, is about 1~1.8 centimetre;Without petal;Stamen is most, flower pesticide yellow; Carpel number piece is from life;Really oblong, is about 1 centimetre, and tip becomes hook-shaped, green.Seed is most, and the kidney shape is long Ellipse, there is longitudinal grin on surface, and brown is glossy;Florescence 4~May;Really phase 6~July.At present, there is no document report Herba Calthae extract has effect of tranquilizing soporific.
Summary of the invention
It is an object of the invention to provide a kind of tranquilizing soporific effect notable, untoward reaction is less, without addicted medicine group Compound and its preparation method and application.
In order to realize the purpose of the present invention, inventor, by lot of experiments research persistent exploration, is finally obtained following skill Art scheme:
A kind of pharmaceutical composition treating insomnia, by Herba Calthae extract and pharmaceutically can adjuvant be prepared from, described The ether extract that Herba Calthae extract is Herba Calthae.It should be noted that according to the common process of formulation art, than Such as direct powder compression, wet granule compression tablet method etc., those skilled in the art is easy to gained Herba Calthae extract The adjuvant available with on pharmaceutics is prepared as the oral formulations commonly used, such as granule, tablet, capsule, pill, oral Liquid etc..Wherein, available on pharmaceutics adjuvant includes filler, disintegrating agent, binding agent, correctives, lubricant.
Present invention also offers the preparation method of described Herba Calthae extract, the method comprises the steps: to weigh Herba Calthae Medical material, loads in reflux, extract, device, adds petroleum ether, put reflux, extract, 1-5 time under 70-80 DEG C of water bath with thermostatic control environment, 0.5-2.5h every time, filters, and filtrate discards after reclaiming petroleum ether, and filtering residue, after volatilization removes petroleum ether, loads backflow and carries During fetching is put, add ether, put reflux, extract, 1-5 time under 38-45 DEG C of water bath with thermostatic control environment, each 0.5-2.5h, filter, Concentrating filter liquor is dried obtains Herba Calthae ether extract.When the present invention prepares Herba Calthae ether extract, selected medicine Material is the herb before cohosh kincup blooms.
Preferably, the preparation method of Herba Calthae extract as above, wherein the addition volume of petroleum ether is quality of medicinal material 5-15 times (L/kg), more preferably 7-8 times (L/kg).
Preferably, the preparation method of Herba Calthae extract as above, wherein the volume that adds of ether is quality of medicinal material 6-12 times (L/kg), more preferably 7-8 times (L/kg).
Preferably, the preparation method of Herba Calthae extract as above, wherein before each reflux, extract, medical material is soaked 5-60min, more preferably 30-40min.
Preferably, the preparation method of Herba Calthae extract as above, the number of times that wherein petroleum ether or aether backflow are extracted For 2-4 time, extraction time successively decreases successively.
In several embodiments on ground preferred for this invention, the preparation method of Herba Calthae extract as above, Qi Zhongshi Oil ether or aether backflow extract number of times be 3 times, the 1st reflux, extract, l.0-1.5h, the 2nd reflux, extract, 0.7-1.0h, 3rd reflux, extract, 0.4-0.6h.
The present invention uses organic solvent to screen Herba Calthae sedative-hypnotic effect position, by a large amount of animal experiment tables Bright, Herba Calthae ether extract prepared by the present invention is the longest to the prolonged sleep time of mice, other solvent extractable matter effects More weak, may be relatively fewer relevant with this extract part amount without effective ingredient or contained effective ingredient.Therefore, this Another bright purpose is to provide a kind of pharmaceutical applications, it may be assumed that above-mentioned Herba Calthae extract is used for tranquilizing soporific in preparation Medicine or health product in application.
It is an advantage of the invention that the effect of tranquilizing soporific is notable, time for falling asleep can not only be shortened, i.e. shorten the sleep derivation phase, And the length of one's sleep can be extended, and deepen Depth of sleep.It addition, the medicine of the present invention is without obvious toxic-side effects, through long-term Use does not results in drug dependence, and raw material sources are extensive simultaneously, and preparation technology is simple, it is not necessary to main equipment, produces into This is low.
Detailed description of the invention
The following is preparation embodiment and the effect test example of each effective extracting section thing dry extract of Herba Calthae of the present invention, to this Bright technical scheme and technique effect are described further and explain.When the present invention prepares Herba Calthae ether extract, selected Medical material be the herb before cohosh kincup blooms.
Embodiment 1: the preparation of Herba Calthae ether extract
Accurately weigh dry Herba Calthae medical material 0.5kg, chopping, load in 6L round-bottomed flask, with 1:8 (kg:L) Solid-liquid ratio add petroleum ether, soak after 30min, put reflux, extract, 3 times in 75 DEG C of thermostat water baths, return for the 1st time Stream extracts lh, the 2nd reflux, extract, 45min, the 3rd reflux, extract, 30min, filters, after filtrate reclaims petroleum ether Discarding, filtering residue, after volatilization removes petroleum ether, loads in 6L round-bottomed flask, adds with the solid-liquid ratio of 1:8 (kg:L) Enter ether, after soaking 30min, put reflux, extract, 3 times in 40 DEG C of thermostat water baths, the 1st reflux, extract, 1h, the 2 reflux, extract, 45min, the 3rd reflux, extract, 30min, to filter, merge 3 extracting solution, filtrate is rotating steaming Sending out decompression and solvent recovery on instrument, concentrated solution obtains dark brown dry extract, is weighed as 27.53g after volatilizing solvent, yield is 5.51%.
Embodiment 2: the preparation of Herba Calthae ether extract
Accurately weigh dry Herba Calthae medical material 1.0kg, chopping, load in 10L round-bottomed flask, with 1:7 (kg:L) Solid-liquid ratio add petroleum ether, soak after 45min, put reflux, extract, 3 times in 75 DEG C of thermostat water baths, return for the 1st time L.5h stream extract, the 2nd reflux, extract, 1h, the 3rd reflux, extract, 30min, filters, and filtrate is abandoned after reclaiming petroleum ether Going, filtering residue, after volatilization removes petroleum ether, loads in 6L round-bottomed flask, adds by the solid-liquid ratio of 1:7 (kg:L) Ether, soaks after 45min, puts reflux, extract, 3 times in 40 DEG C of thermostat water baths, the 1st reflux, extract, 1.5h, and the 2nd Secondary reflux, extract, 1h, the 3rd reflux, extract, 30min, to filter, merge 3 extracting solution, filtrate is on a rotary evaporator Decompression and solvent recovery, concentrated solution obtains dark brown dry extract, is weighed as 53.70g after volatilizing solvent, yield is 5.37%.
Comparative example 1: the preparation of Herba Calthae ethanol extraction
Accurately weigh dry Herba Calthae medical material 0.5kg, chopping, load in 6L round-bottomed flask, with 1:8 (kg:L) Solid-liquid ratio add petroleum ether, soak after 30min, put reflux, extract, 3 times in 75 DEG C of thermostat water baths, return for the 1st time Stream extracts lh, the 2nd reflux, extract, 45min, the 3rd reflux, extract, 30min, filters, after filtrate reclaims petroleum ether Discarding, filtering residue, after volatilization removes petroleum ether, loads in 6L round-bottomed flask, adds by the solid-liquid ratio of 1:8 (kg:L) Enter ethanol, after soaking 30min, put reflux, extract, 3 times in 90 DEG C of thermostat water baths, the 1st reflux, extract, 1h, the 2 reflux, extract, 45min, the 3rd reflux, extract, 30min, to filter, merge 3 extracting solution, filtrate is rotating steaming Sending out decompression and solvent recovery on instrument, concentrated solution obtains dark brown dry extract, is weighed as 60.18g after volatilizing solvent, yield is 12.04%.
Comparative example 2: the preparation of Herba Calthae ethyl acetate extract
Accurately weigh dry Herba Calthae medical material 0.5kg, chopping, load in 6L round-bottomed flask, with 1:8 (kg:L) Solid-liquid ratio add petroleum ether, soak after 30min, put reflux, extract, 3 times in 75 DEG C of thermostat water baths, return for the 1st time Stream extracts lh, the 2nd reflux, extract, 45min, the 3rd reflux, extract, 30min, filters, after filtrate reclaims petroleum ether Discarding, filtering residue, after volatilization removes petroleum ether, loads in 6L round-bottomed flask, adds with the solid-liquid ratio of 1:8 (kg:L) Enter ethyl acetate, after soaking 30min, put reflux, extract, 3 times in 85 DEG C of thermostat water baths, the 1st reflux, extract, 1h, 2nd reflux, extract, 45min, the 3rd reflux, extract, 30min, to filter, merge 3 extracting solution, filtrate is rotating Decompression and solvent recovery on evaporimeter, concentrated solution obtains dark brown dry extract, is weighed as 31.44g after volatilizing solvent, yield is 6.29%.
The experimental study to Sedative And Hypnotic Effect of the embodiment 3 Herba Calthae extract
Cleaning grade Kunming mouse 50, male and female half and half, body weight (20 ± 2) g.It is randomly divided into blank group, positive control Group, ether extract group, ethanol extraction group, ethyl acetate extract group, often 10 animals of group, male and female half and half.Second Ether extract group gives the Herba Calthae ether extract 40.0mg/kg of the embodiment of the present invention 1 preparation, and ethanol extraction group gives The Herba Calthae ethanol extraction 40.0mg/kg of above-mentioned comparative example 1 preparation, ethyl acetate extract group gives above-mentioned contrast The Herba Calthae ethyl acetate extract 40.0mg/kg of embodiment 2 preparation, positive controls gives diazepam 2mg/kg, blank Matched group gives isopyknic normal saline;The equal gastric infusion of each group, every day 1 time, continuous 3 days, gavage volume 15ml/kg. Stand number of times and the activity time of 5min after putting into case with mice autonomic activities instrument record mice after being administered 60min in second day Number.After last is administered 60min, each group mice equal lumbar injection pentobarbital sodium 50mg/kg, sleep disappears with righting reflex Losing is index, keeps more than 30s person with the downward posture of animal back, it is judged that for righting reflex loss, record injection penta bar ratio To mice sleeping duration as dropping asleep latency after appropriate sodium, and observed and recorded righting reflex loss to awakening time Between as the prolonged sleep time.
By the result of the test of table 1 it can be seen that except ether extraction beyond the region of objective existence, the solvent extractable matter of other Herba Calthaes is to normally Mice autonomic activities, almost without impact, improves the frequency of mice autonomic activities the most to a certain extent;It addition, holding Continuing the aspect length of one's sleep, ether extract, ethanol extraction and ethyl acetate extract group compare the brightest with blank group Aobvious prolongation, but only ether extract group is the most notable on the impact of prolonged sleep time, compares with blank group and has Pole significant difference (P < 0.01), compares with positive controls and has significant difference (P < 0.05), and ether carries simultaneously Take thing group and shorten dropping asleep latency, compare with blank group or positive controls and be respectively provided with significant difference (P<0.05)。
Table 1 is respectively organized mice autonomic activities and compares the length of one's sleep
Compare with blank group,P < 0.05,★★P < 0.01;Compare with positive controls,P < 0.05,▼▼P < 0.01.

Claims (8)

1. the pharmaceutical composition treating insomnia, by Herba Calthae extract and pharmaceutically can adjuvant be prepared from, it is characterized in that, the described ether extract that Herba Calthae extract is Herba Calthae, prepare as follows: weigh Herba Calthae medical material, load in reflux, extract, device, add petroleum ether, put reflux, extract, 1-5 time under 70-80 DEG C of water bath with thermostatic control environment, 0.5-2.5h every time, filter, filtrate discards after reclaiming petroleum ether, filtering residue is after volatilization removes petroleum ether, load in reflux, extract, device, add ether, put reflux, extract, 1-5 time under 38-45 DEG C of water bath with thermostatic control environment, 0.5-2.5h every time, filter, concentrating filter liquor is dried obtains Herba Calthae ether extract.
The preparation method of Herba Calthae extract the most according to claim 1, it is characterized in that, the method comprises the steps: to weigh Herba Calthae medical material, load in reflux, extract, device, add petroleum ether, put reflux, extract, 1-5 time under 70-80 DEG C of water bath with thermostatic control environment, 0.5-2.5h every time, filter, filtrate discards after reclaiming petroleum ether, filtering residue is after volatilization removes petroleum ether, load in reflux, extract, device, add ether, put reflux, extract, 1-5 time under 38-45 DEG C of water bath with thermostatic control environment, 0.5-2.5h every time, filter, concentrating filter liquor is dried obtains Herba Calthae ether extract.
The preparation method of Herba Calthae extract the most according to claim 2, it is characterised in that the volume that adds of petroleum ether is 5-15 times of quality of medicinal material.
The preparation method of Herba Calthae extract the most according to claim 2, it is characterised in that the volume that adds of ether is 6-12 times of quality of medicinal material.
The preparation method of Herba Calthae extract the most according to claim 2, it is characterised in that every time before reflux, extract, medical material is soaked 5-60min.
The preparation method of Herba Calthae extract the most according to claim 2, it is characterised in that the number of times that petroleum ether or aether backflow are extracted is 2-4 time, and extraction time successively decreases successively.
The preparation method of Herba Calthae extract the most according to claim 6, it is characterised in that the number of times that petroleum ether or aether backflow are extracted is 3 times, the 1st reflux, extract, l.0-1.5h, the 2nd reflux, extract, 0.7-1.0h, the 3rd reflux, extract, 0.4-0.6h.
8. the Herba Calthae extract described in claim 1 is in the application prepared in the medicine or health product of tranquilizing soporific.
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Inventor after: Shang Yimei

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