CN109692191A - Application of the Cortex Ilicis Rotundae extract in the drug that preparation promotes sleep - Google Patents
Application of the Cortex Ilicis Rotundae extract in the drug that preparation promotes sleep Download PDFInfo
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Abstract
The present invention provides a kind of application of Cortex Ilicis Rotundae extract in the drug that preparation promotes sleep.Iron holly bark is as a kind of medical herb that medical usage is very extensive, its extract, especially total saponin extracts, more preferably, Peltatin glucoside in total saponin extracts can significantly improve insomnia caused by yellow Jackets in terms of promoting sleep, time for falling asleep can not only be shortened, and be able to extend sleeping time.As it can be seen that the application provides a kind of new application of Cortex Ilicis Rotundae extract in terms of promoting sleep, the preparation for current promotion sleep drug provides the new selection of one kind.
Description
Technical field
The present invention relates to the novel medical use fields of Cortex Ilicis Rotundae extract, in particular to a kind of Cortex Ilicis Rotundae extract
Application in the drug that preparation promotes sleep.
Background technique
Iron holly bark derives from the dry bark also known as rough gentian of holly plant ilexrotunda (llex rotunda Thunb)
Young, white agalloch eaglewood, silver, white orchid are fragrant, bullshit wood, bear gall wood, Chinese ilex is young, broken bone is wooden, small wind rattan, Bai Fanmu, ninebark, cross mountain
Wind, red bear gall, Chinese ilex bavin, mountain Chinese ilex, white Pi Dongqing, Cortex Ilicis Rotundae etc..Ilexrotunda is grown on deserted mountain sparse woods, hills or small stream side,
It is distributed mainly on the provinces and regions such as Guangdong, Guangxi, Fujian, Taiwan, Yunnan, Jiangsu, Zhejiang, Anhui, Jiangxi, Hunan.It is bitter, cold in nature,
There are clearing heat and detoxicating, swelling and pain relieving, dampness removing, wind-dispelling relieving summer-heat and other effects, record in " south of the Five Ridges gather medicinal herbs record ", claims " from radix aucklandiae, bitter, clear
Heat toxin " is southern region of China traditional herbal medicine (Huang Wenjian, the Popular Utilization of iron holly bark, Jiangxi traditional Chinese medicine, 1996,2:147).
Iron holly bark bark contains flavonoid glycoside, phenols, tannin, triterpene glycosides.Rotundic acid, that is, rotundic acid, tool in iron holly bark are dwelt
Ilexin, that is, pedunculoside, containing containing rotundic acid isopropylidene ketal, Syringin, sinapyladehyde, sinapyladehyde in iron holly bark
Glucoside, syringaldehyde and 3 one acetyloleanolic acids and stearic acid.Clinically be usually used in flu, tonsillitis, sphagitis,
Traumatic injury, carbuncle furuncle sore, traumatic hemorrhage, burn, scald etc. are controlled in acute gastroenteritis, dysentery, ostalgia etc., external application.
Studies have shown that rotundic acid, which has, to be improved myocardial ischemia, reduces myocardial infarction area, improve hypoxia-bearing capability, is bright
It is aobvious to reduce blood contrast viscosity and blood plasma specific viscosity, the effect for improving cerebral ischemia, reduction brain infarction area.He Bing etc. studies have shown that
Iron holly bark ethanol crude extract has significantly reduction coronary flow, reducing heart rate and weakens myocardial contractive power, improves resistance to lack
Oxygen ability, water crude extract can also reduce coronary flow, improve hypoxia-bearing capability and antiarrhythmic effect, but reducing heart rate and
Keep mental and physical efforts abated effect unobvious.Chen little Xia is research shows that there is iron holly bark n-butanol extract anti-arrhythmia and anti-cardiac muscle to lack
Blood effect.Pang little Xiong etc. reports the separation and identification of pedunculoside in iron holly bark, takes iron holly bark powder with 95% alcohol reflux
It extracts, is concentrated into small size, the distilled water of equivalent is added, stands overnight, be centrifuged, sediment three times with appropriate washing, use by crude product
Chloroform degreasing obtains Peltatin glucoside by silica gel column chromatography.
Contain a large amount of pentacyclic triterpene saponins in iron holly bark, it was reported that wherein the content of Peltatin glucoside is up to
8.8%, if adding the content of its aglycon rotundic acid, total saponin content is higher.Iron holly bark medicinal material has recorded in
In state's pharmacopeia 2010 editions one, page 293, the content of its pedunculoside of States Pharmacopoeia specifications must not be lower than 4%, and Syringin content is not
It obtains and is lower than 1%.Mainly treatment gastroenteritis is made with its water extract in medicinal material at present, and the Chinese patent drug of the diseases such as indigestion is such as rescued
Tabellae contragasteralgiam, compound iron holly bark capsule, fukean tablet, suitable capsule of stomach etc. must be answered.Iron holly bark medicinal material water extraction method, is mainly extracted
Water soluble ingredient Syringin in iron holly bark, and there is also have many pentacyclic triterpene saponins not extract completely in the dregs of a decoction.
Iron holly bark is the medicinal material for having extensive use, and Chinese patent application CN101032534A discloses jiubiying total glycosides
Preparation method and application in diseases of cardiovascular and cerebrovascular systems.Chinese patent application CN101342186A discloses pedunculoside
(pedunculoside) for treating hyperlipidemia, Chinese patent application CN101033245A also discloses pedunculoside can
For treating coronary heart disease, angina pectoris, apoplexy, the diseases of cardiovascular and cerebrovascular systems such as cerebral infarction, Chinese patent application CN101342186A
Rotundic acid (Rotundic acid) is disclosed for treating hyperlipidemia, Acta Pharmaceutica Sinica, 1980,15 (5): 303-305 report
Syringin has anastalsis, and external medicine, traditional Chinese medicine fascicle, 2000,22 (6): 346-347 reports Syringin
With hepatoprotective effect, document PlantaMed., 2004,70:1027-1032 report Syringin again makees with anti-inflammatory and antalgic
With.
But in summary various uses finds no the report that this medicinal material of iron holly bark acts in terms of promoting sleep.
Summary of the invention
The main purpose of the present invention is to provide a kind of Cortex Ilicis Rotundae extracts to promote the application in the drug slept in preparation,
To promote sleep to provide a kind of new way, and widen the medical value of this medicinal material of iron holly bark.
To achieve the goals above, the present invention provides a kind of Cortex Ilicis Rotundae extracts in the drug that preparation promotes sleep
Using.
Further, Cortex Ilicis Rotundae extract includes general saponin of cortex ilecis rotundae.
Further, Cortex Ilicis Rotundae extract includes Peltatin glucoside.
Further, the dosage of general saponin of cortex ilecis rotundae is 100~200mg/kg.
Further, the dosage of Peltatin glucoside is 50~100mg/kg.
Further, the administration mode of drug is oral administration.
Further, the dosage form of drug is tablet, particle, capsule or oral solution.
It applies the technical scheme of the present invention, iron holly bark is extracted as a kind of medical herb that medical usage is very extensive
Object, especially total saponin extracts, it is further preferred that the Peltatin glucoside in total saponin extracts can be significant in terms of promoting sleep
Improve insomnia caused by yellow Jackets, time for falling asleep can not only be shortened, and be able to extend sleeping time.As it can be seen that this Shen
The new application in terms of promoting sleep please provides a kind of new medical usage for Cortex Ilicis Rotundae extract, while being also current rush
A kind of new selection is provided into sleep drug.
Specific embodiment
It should be noted that in the absence of conflict, the features in the embodiments and the embodiments of the present application can phase
Mutually combination.Below in conjunction with embodiment, the present invention will be described in detail.
As background technique is previously mentioned, the prior art has many grind to the medical usage of this medical herb of iron holly bark
Study carefully and reports.But in current research, it is not found its medical value in terms of promoting sleep.And the application passes through to existing
The medical value for the single component Peltatin glucoside in general saponin of cortex ilecis rotundae and general saponin of cortex ilecis rotundae for thering is extracting method to obtain
It is furtherd investigate, discovery Cortex Ilicis Rotundae extract can effectively facilitate sleep.It is specific as follows:
The application will be by that containing general saponin of cortex ilecis rotundae extract or will contain the Cortex Ilicis Rotundae extract pair of Peltatin glucoside
Insomnia mouse model (pass through injection yellow Jackets and obtain insomnia mouse model) is handled, through with blank group it was found that,
The mouse for giving general saponin of cortex ilecis rotundae extract or the Cortex Ilicis Rotundae extract processing group containing Peltatin glucoside enters sleep
Time is obviously shortened, while the sleep time entered after sleep also significantly extends, thus, it has obtained and has contained jiubiying total soap
Glucoside extract or Cortex Ilicis Rotundae extract containing Peltatin glucoside have the sleep state for improving insomnia mouse, it is promoted to sleep
It sleeps.
Based on the discovery, in a kind of typical embodiment of the application, provides a kind of Cortex Ilicis Rotundae extract and preparing
Promote the application in the drug of sleep.
Cortex Ilicis Rotundae extract in the application can use various known method and obtain or prepare.It should be noted that
It is exactly alcohol extracting since the current extracting method of Cortex Ilicis Rotundae extract is not that water mentions, regardless of the extract is that alcohol extract or water mention
Object, main component therein all include general saponin of cortex ilecis rotundae.Thus, the Cortex Ilicis Rotundae extract in the application refers to existing known method
Extract obtained various extracts, can also refer to the general saponin of cortex ilecis rotundae extract improved on the basis of existing method or
Peltatin glucoside.
Iron holly bark is as a kind of medical herb that medical usage is very extensive, extract, especially total saponin extracts,
It is further preferred that the Peltatin glucoside in total saponin extracts can be significantly improved and be lost caused by yellow Jackets in terms of promoting sleep
It sleeps, time for falling asleep can not only be shortened, and be able to extend sleeping time.As it can be seen that this application provides a kind of extractions of iron holly bark
New application of the object in terms of promoting sleep, the preparation for current promotion sleep drug provide a kind of new selection.
In a preferred embodiment of the present application, above-mentioned Cortex Ilicis Rotundae extract is general saponin of cortex ilecis rotundae.Jiubiying total soap
Glycosides can extract preparation using existing method, one of preferred the preparation method is as follows: iron holly bark coarse powder is taken, with 2~10
The alcohol reflux of 50~95% (volume contents) again extracts three times, and 1~3 hour every time, combined extract was concentrated into medicinal extract,
Then plus 3~10 in the water of medicinal extract volume, heats, and stirring is stood overnight, and is centrifuged, when supernatant is concentrated into 0.5~2 times of volume,
It is cooled to room temperature, is centrifuged, sediment is flushed three times with suitable quantity of water, is dried to obtain general saponin of cortex ilecis rotundae.
In the application another kind preferred embodiment, above-mentioned Cortex Ilicis Rotundae extract is Peltatin glucoside.Peltatin glucoside
For one of general saponin of cortex ilecis rotundae ingredient.Peltatin glucoside can be obtained using existing preparation method, one of preferred
The preparation method is as follows: take iron holly bark coarse powder, extracted three times with the alcohol reflux of 2~10 times of 50~95% (volume contents),
1~3 hour every time, combined extract was concentrated into medicinal extract, and then plus 3~10 in the water of medicinal extract volume, heated, stirring was stood
Night, centrifugation obtain sediment and supernatant.Sediment adds the alcohol reflux of 50~95% (volume contents) to extract, filtering, filtrate
Concentration is placed, and filtering, drying precipitate obtains a part of total saposins.Total saposins add 10~100 times 50~95% (volume contains
Amount) alcohol crystal, obtain a part of Peltatin glucoside crude product.When supernatant is concentrated into 0.5~2 times of volume, it is cooled to room temperature, from
The heart, sediment are flushed three times with suitable quantity of water, dry, and 50~95% (volume content) alcohol crystals measured with 10~100 times obtain
Another part Peltatin glucoside crude product.Peltatin glucoside obtained merges twice, 50~95% (volumes measured with 10~100 times
Content) ethyl alcohol repeated recrystallize, obtaining Peltatin glucoside sterling, (wherein, 98.0%) mass content of Peltatin glucoside is greater than.
The application application in, can by Cortex Ilicis Rotundae extract and other promote sleep drug combination, such as with its
There is the drug for promoting sleep to be combined for he, can obtain the effect that collaboration promotes sleep.
In the above-mentioned application of the application, said medicine dosage can pacify in the administration of the exercise use of two kinds of drugs
It carries out reasonably adjusting optimization on the basis of full dosage and obtain.Promote in sleep application specific, dosage can be according to as follows
Factor and become: individual morbid state, age, gender, weight and drug causes the ability of desired response in individual.
For any specific subject, given dose can be adjusted according to the professional judgment of individual need and application people at any time.
In a preferred embodiment of the present application, Cortex Ilicis Rotundae extract is general saponin of cortex ilecis rotundae, general saponin of cortex ilecis rotundae
Dosage is 100~200mg/kg.In another preferred embodiment, Cortex Ilicis Rotundae extract is Peltatin glucoside, has the Chinese ilex that dwells
The dosage of glycosides is 50~100mg/kg.
General saponin of cortex ilecis rotundae is when dosage is respectively lowest dose level 100mg/kg and maximum dose level 200mg/kg, tool
When ilexin dosage of dwelling is respectively lowest dose level 50mg/kg and maximum dose level 100mg/kg, amobarbital can be shortened
Sodium above threshold dosage or above threshold dropping asleep latency caused by dosage, while the sleeping time of mouse can also be extended, thus above two
Cortex Ilicis Rotundae extract can improve insomnia caused by yellow Jackets, and play the role of promoting sleep.If jiubiying total soap
It is same that there is promotion sleep when the dosage of glycosides is lower than 100mg/kg or when Peltatin glucoside dosage is lower than 50mg/kg
Effect, only facilitation effect is slightly weak.And the dosage of general saponin of cortex ilecis rotundae be higher than 200mg/kg when or Peltatin glucoside give
When pharmaceutical quantities are higher than 100mg/kg, equally have the function of promoting sleep, be only possible to have potential drug risk.
In above-mentioned application, the pharmaceutical administration containing Cortex Ilicis Rotundae extract is carried out according to the dosage form of its specific drug
Selection.It is preferred that the administration mode of above-mentioned Cortex Ilicis Rotundae extract is oral administration.And preferably, the dosage form of drug be tablet,
Particle, capsule or oral solution.Cortex Ilicis Rotundae extract is prepared into above-mentioned common dosage form, the existing medicine can be made full use of
Object administration mode.
Illustrate the discovery of the application below in conjunction with specific pharmacodynamic experiment and its in terms of improving and promoting sleep
Beneficial effect.
Experiment one cooperates with above threshold yellow Jackets sleep laboratory
1.1 method
Take weight 18~22g mouse, half male and half female is grouped at random by weight, respectively blank group, stable 2mg/kg group,
Peltatin glucoside low dosage (50mg/kg) group, high dose (100mg/kg) group, general saponin of cortex ilecis rotundae low dosage (100mg/kg)
Group, high dose (200mg/kg) group.
Bare substrate, stable, Peltatin glucoside, general saponin of cortex ilecis rotundae are gavaged respectively in experimental day, are according to dosage administered one
Secondary, administered volume is 0.2ml/10g weight.
Yellow Jackets 35mg/kg (0.1ml/10g) is injected intraperitoneally after 40min is administered, mouse rights instead after observation injection
Disappearance and recovery situation are penetrated, and records time for falling asleep and recovery time, calculates dropping asleep latency and sleep time (if animal
Righting reflex does not disappear in 1h, and dropping asleep latency is denoted as 60min, and sleep time is denoted as 0min).Dropping asleep latency and
The calculation formula difference of sleep time is as follows:
Dropping asleep latency (min)=sleeping duration-intraperitoneal injection yellow Jackets time.
Sleep time (min)=recovery time-sleeping duration.
Then for statistical analysis with t inspection, compare group difference.Statistical result is shown in Table 1.
Table 1: Peltatin glucoside to above threshold dose of sodium pentobarbitone cause sleeping time influence (N=16)
Compared with blank control group, P < 0.01 * *；*P<0.05.
1.2 result
From table 1 it follows that there were significant differences for the statistical result of four dosage groups.General saponin of cortex ilecis rotundae is giving medicament
Amount is respectively 100mg/kg and 200mg/kg, when Peltatin glucoside dosage is respectively 50mg/kg and 100mg/kg, can be contracted
Short yellow Jackets above threshold dropping asleep latency caused by dosage, while the sleeping time of mouse can also be extended.As it can be seen that can be significant
Promote sleep, improves insomnia caused by yellow Jackets.
The hypnosis test of yellow Jackets under two collaboration threshold of experiment
2.1. method
Female mice is grouped at random by weight, respectively blank group, stable 2mg/kg group, Peltatin glucoside low dosage
(50mg/kg) group, high dose (100mg/kg) group, general saponin of cortex ilecis rotundae low dosage (100mg/kg) group, high dose (200mg/
Kg) group.
Bare substrate, stable, Peltatin glucoside and general saponin of cortex ilecis rotundae are gavaged respectively in experimental day, are according to dosage administered one
Secondary, administered volume is 0.2ml/10g weight.
Yellow Jackets 24mg/kg (0.1ml/10g) is injected intraperitoneally after 40min is administered.1h varus is positive and negative after observation injection
The number of animals of disappearance is penetrated, and records time for falling asleep and recovery time, calculates dropping asleep latency and sleep time (if animal turns over
Positive reflection does not disappear in 1h, and dropping asleep latency is denoted as 60min, and sleep time is denoted as 0min).It dropping asleep latency and sleeps
The calculation formula difference of dormancy duration is as follows:
Dropping asleep latency (min)=sleeping duration-intraperitoneal injection yellow Jackets time.
Sleep time (min)=recovery time-sleeping duration.
The number of animals Chi-square Test of righting reflex loss is for statistical analysis, the group difference compared with blank group；It falls asleep
Incubation period and sleep time are for statistical analysis with t inspection, compare group difference.Statistical result is shown in Table 2.
Influence of 2 Peltatin glucoside of table to yellow Jackets syngignoscism under threshold
Compared with blank control group, P < 0.001 * * *；**P<0.01；*P<0.05.
2.2. result
From Table 2, it can be seen that general saponin of cortex ilecis rotundae is respectively 100mg/kg and 200mg/kg in dosage, tool is dwelt the winter
When green glycosides dosage is respectively 50mg/kg and 100mg/kg, sleep can be remarkably promoted, so that sleep number of animals are significant
Increase.And dropping asleep latency caused by yellow Jackets sub-threshold dose can be shortened, while can also significantly extend sleeping time,
Therefore, in terms of promoting animal sleep, the sleep state of insomnia mouse model caused by yellow Jackets can be improved.
It should be noted that giving penta bar of above threshold dosage and sub-threshold dose to mouse in above-mentioned experiment one and experiment two
Effect than appropriate sodium is to establish insomnia mouse model,
It can be seen from the above description that the above embodiments of the present invention realized the following chievements: iron holly bark is made
For a kind of medical herb that medical usage is very extensive, extract, especially total saponin extracts, it is further preferred that total saposins mention
The Peltatin glucoside in object is taken, in terms of promoting sleep, insomnia caused by yellow Jackets can be significantly improved, can not only be shortened
Time for falling asleep, and it is able to extend sleeping time.As it can be seen that this application provides a kind of Cortex Ilicis Rotundae extracts in terms of promoting sleep
New application, the preparation for current promotion sleep drug provides the new selection of one kind.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field
For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any to repair
Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (7)
1. application of the Cortex Ilicis Rotundae extract in the drug that preparation promotes sleep.
2. application according to claim 1, which is characterized in that the Cortex Ilicis Rotundae extract includes general saponin of cortex ilecis rotundae.
3. application according to claim 2, which is characterized in that the Cortex Ilicis Rotundae extract includes Peltatin glucoside.
4. application according to claim 2, which is characterized in that the dosage of the general saponin of cortex ilecis rotundae be 100~
200mg/kg。
5. application according to claim 3, which is characterized in that the dosage of the Peltatin glucoside is 50~100mg/
kg。
6. application according to any one of claim 1 to 5, which is characterized in that the administration mode of the drug is oral
Administration.
7. application according to any one of claim 1 to 5, which is characterized in that the dosage form of the drug be tablet,
Particle, capsule or oral solution.
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