CN109692191B - Application of ovateleaf holly bark extract in preparation of sleep-promoting medicine - Google Patents
Application of ovateleaf holly bark extract in preparation of sleep-promoting medicine Download PDFInfo
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Abstract
The invention provides application of an ovateleaf holly bark extract in preparing a medicine for promoting sleep. The ilex rotundifolia is used as a medicinal plant with wide medical application, and the extract, particularly the total saponin extract, more preferably the pedunculoside in the total saponin extract can not only shorten the time of falling asleep, but also prolong the sleep time in the aspect of promoting sleep. Therefore, the application provides a new application of the ovateleaf holly bark extract in the aspect of promoting sleep, and provides a new choice for the preparation of the existing sleep-promoting medicine.
Description
Technical Field
The invention relates to the field of new medical application of an ovate leaf holly bark extract, and particularly relates to application of the ovate leaf holly bark extract in preparing a medicine for promoting sleep.
Background
Cortex Ilicis Rotundae is derived from dried bark of ilex rotunda Thunb (Aquifoliaceae), radix Gentianae, lignum Aquilariae Resinatum, silver, herba Brandisiae Hancei, herba Selaginellae Canadensis, fel Ursi, fructus Ilicis Purpureae, ramulus Sambuci Williamsii, caulis Sinomenii, radix et folium Fraxini, cortex Melaleucae leucadendrae, herba Ursus domestica, radix Ilicis Pubescentis, and radix Ilicis Pubescentis. The ilex latifolia grows on barren mountain sparse forest, hills or streams and is mainly distributed in provinces such as Guangdong, Guangxi, Fujian, Taiwan, Yunnan, Jiangsu, Zhejiang, Anhui, Jiangxi, Hunan and the like. Bitter in taste and cold in nature, has the efficacies of clearing away heat and toxic material, relieving swelling and pain, promoting diuresis, dispelling wind and relieving summer heat and the like, is recorded in Lingnan medicine gathering book, and is called 'Saikou, bitter in taste and clearing away heat and toxic material' as folk herbal medicine in southern areas of China (Huang Wen Ke, folk application of ovate holly, Jiangxi traditional Chinese medicine, 1996, 2: 147).
Cortex Ilicis Rotundae contains flavonoid glycoside, phenols, tannin, and triterpene glycoside. The cortex Ilicis Rotundae contains iron wintergreen acid (ilexolic acid), pedunculoside (pedunculoside), and contains isopropyl idene ketoketal, syringin, sinapine aldehyde glucoside, syringaldehyde, 3-acetyl oleanolic acid and stearic acid. It is used for treating common cold, tonsillitis, pharyngolaryngitis, acute gastroenteritis, dysentery, osteodynia, etc., and can be used for treating traumatic injury, carbuncle, furuncle, pyocutaneous disease, traumatic hemorrhage, burn, scald, etc.
Research shows that the rotundic acid has the effects of improving myocardial ischemia, reducing myocardial infarction area, improving anoxia resistance, obviously reducing whole blood specific viscosity and plasma specific viscosity, improving cerebral ischemia and reducing cerebral infarction area. The research on ice and the like shows that the rotundifolia crude ethanol extract has obvious effects of reducing coronary flow, slowing heart rate, weakening myocardial contractility and improving anoxia resistance, and the aqueous crude extract can also reduce coronary flow, improve anoxia resistance and resist arrhythmia, but has no obvious effects of slowing heart rate and weakening heart rate. Studies of Chenxiaxia show that the n-butyl alcohol extract of the rotundifolia has the effects of resisting arrhythmia and myocardial ischemia. Poncirus trifoliata et al report the separation and identification of pedunculoside in ovate leaf holly bark, reflux-extracting ovate leaf holly bark powder with 95% ethanol, concentrating to a small volume, adding an equal amount of distilled water, standing overnight, centrifuging, washing precipitate with an appropriate amount of water for three times, degreasing crude product with chloroform, and performing silica gel column chromatography to obtain pedunculoside.
Ilicis rotunda Rotundifolia contains a large amount of pentacyclic triterpenoid saponins, and the content of pedunculoside is reported to be as high as 8.8%, and if the content of aglycon ilexolic acid is added, the content of total saponins is higher. The ovateleaf holly bark medicinal materials are collected in the first part of the 2010 edition of the Chinese pharmacopoeia, page 293, which specifies that the content of pedunculoside is not less than 4% and the content of syringin is not less than 1%. At present, the medicinal materials are mainly prepared into Chinese patent medicines for treating gastroenteritis, dyspepsia and other diseases by using water extracts of the medicinal materials, such as ovate leaf holly bark stomachache tablets, compound ovate leaf holly bark capsules, fukean tablets, gastrointestinal capsules and the like. The water extraction method of the ovateleaf holly bark medicinal material mainly extracts the water-soluble ingredient syringin in the ovateleaf holly bark, and a lot of pentacyclic triterpenoid saponins existing in medicine dregs are not completely extracted.
The rotunda thunb is a medicinal material with wide application, and Chinese patent application CN101032534A discloses a preparation method of rotunda thunb total glycosides and application of the rotunda thunb total glycosides in cardiovascular and cerebrovascular system diseases. Chinese patent application CN101342186A discloses pedunculoside for treating hyperlipidemia, chinese patent application CN101033245A also discloses pedunculoside for treating cardiovascular and cerebrovascular diseases such as coronary heart disease, angina pectoris, apoplexy, cerebral infarction, etc., chinese patent application CN101342186A discloses Rotundic acid for treating hyperlipidemia, pharmaceutics, 1980, 15 (5): 303-305 reports that syringin has hemostatic effect, and the traditional Chinese medicine is classified in foreign medicine, 2000, 22 (6): 346-347 reports that syringin has hepatoprotective effect, and the literature plantamed, 2004, 70: 1027 and 1032 further report that syringin has anti-inflammatory and analgesic effects.
However, no report that the ovate leaf holly bark has the function of promoting sleep is found in combination of the above various applications.
Disclosure of Invention
The invention mainly aims to provide the application of the ovateleaf holly bark extract in preparing the medicine for promoting sleep, provides a new way for promoting sleep and widens the medicinal value of the ovateleaf holly bark extract.
In order to achieve the purpose, the invention provides application of an ovateleaf holly bark extract in preparing a medicine for promoting sleep.
Further, the extract of ovateleaf holly bark comprises ovateleaf holly bark total saponins.
Further, the extract of Ilicis cortex Ilicis Rotundae comprises pedunculoside.
Further, the administration dosage of the ilex rotunda thunb total saponin is 100-200 mg/kg.
Further, the administration dosage of the pedunculoside is 50-100 mg/kg.
Further, the mode of administration of the drug is oral administration.
Further, the preparation form of the medicine is tablets, granules, capsules or oral liquid.
By applying the technical scheme of the invention, the ovateleaf holly bark is used as a medicinal plant with wide medical application, and the extract, especially the total saponin extract, more preferably the pedunculoside in the total saponin extract can not only shorten the time of falling asleep, but also prolong the sleep time in the aspect of promoting sleep. Therefore, the new application of the holly bark extract in the aspect of promoting sleep provides a new medical application of the holly bark extract, and simultaneously provides a new choice for the current sleep-promoting medicine.
Detailed Description
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail with reference to examples.
As mentioned in the background, there have been many studies and reports on the medical use of ovate leaf holly bark as a medicinal plant in the prior art. However, no medical value of the traditional Chinese medicine composition in promoting sleep is found in the current research. According to the application, the ilex rotundifolia thumb total saponins obtained by the existing extraction method and the medicinal value of the ilex rotundifolia thumb total saponins containing the single component of pedunculoside are deeply researched, and the ilex rotundifolia thumb extract can effectively promote sleep. The method comprises the following specific steps:
the mice injected with pentobarbital sodium are treated by the ovate leaf holly bark extract containing the ovate leaf holly bark total saponin extract or the ovate leaf holly bark extract containing the roost holly bark glycoside, and the comparison with a blank group shows that the time of the mice in the treatment group of the ovate leaf holly bark total saponin extract or the ovate leaf holly bark extract containing the ovate leaf holly bark extract for sleeping is obviously shortened, and the sleeping duration time after the mice in sleeping is also obviously prolonged, so that the ovate leaf holly bark total saponin extract or the ovate leaf holly bark extract containing the ovate leaf holly bark extract has the effects of improving the sleeping condition of the insomnia mice and promoting the sleeping of the insomnia mice.
Based on this finding, in one exemplary embodiment of the present application, there is provided a use of an extract of ovateleaf holly bark for preparing a sleep-promoting drug.
The extract of cortex Ilicis Rotundae in this application can be obtained or prepared by known method. It should be noted that, because the existing extraction method of the ovateleaf holly bark extract is not aqueous extraction or alcohol extraction, the main component of the ovateleaf holly bark extract contains ovateleaf holly bark total saponins regardless of whether the extract is an alcohol extract or an aqueous extract. Thus, the extract of ovateleaf holly bark in the present application refers to various extracts obtained by the existing known methods, and can also refer to the total saponin extract of ovateleaf holly bark or pedunculoside obtained by improving the existing methods.
The ilex rotundifolia is used as a medicinal plant with wide medical application, and the extract, particularly the total saponin extract, more preferably the pedunculoside in the total saponin extract can not only shorten the time of falling asleep, but also prolong the sleep time in the aspect of promoting sleep. Therefore, the application provides a new application of the ovateleaf holly bark extract in the aspect of promoting sleep, and provides a new choice for the preparation of the existing sleep-promoting medicine.
In a preferred embodiment of the present application, the extract of ovateleaf holly bark is ovateleaf holly bark total saponins. The ilex rotunda thunb total saponin can be extracted and prepared by the existing method, wherein one preferable preparation method comprises the following steps: taking ovateleaf holly bark coarse powder, performing reflux extraction for three times by using 2-10 times of 50-95% (volume content) ethanol for 1-3 hours each time, combining extracting solutions, concentrating to obtain an extract, then adding 3-10 times of water in the volume of the extract, heating, stirring, standing overnight, centrifuging, concentrating supernate to 0.5-2 times of the volume, cooling to room temperature, centrifuging, washing precipitates with proper amount of water for three times, and drying to obtain ovateleaf holly bark total saponins.
In another preferred embodiment of the present invention, the extract of Ilicis cortex is pedunculoside. Ilexoside is one component of cortex Ilicis Rotundae total saponin. Pedunculoside can be obtained by conventional methods, and one preferred method is as follows: taking ovate leaf holly bark coarse powder, performing reflux extraction for three times by using 2-10 times of 50-95% (volume content) ethanol, performing 1-3 hours each time, combining extracting solutions, concentrating to obtain an extract, then adding 3-10% of water in the volume of the extract, heating, stirring, standing overnight, and centrifuging to obtain a precipitate and a supernatant. And (3) adding 50-95% (volume content) of ethanol into the precipitate, performing reflux extraction, filtering, concentrating the filtrate, standing, filtering, and drying the precipitate to obtain a part of total saponins. Adding 10-100 times of 50-95% (volume content) ethanol into the total saponin for crystallization to obtain a part of pedunculoside crude product. Concentrating the supernatant to 0.5-2 times of volume, cooling to room temperature, centrifuging, washing the precipitate with a proper amount of water for three times, drying, and crystallizing with 10-100 times of 50-95% (volume content) ethanol to obtain the other part of the pedunculoside crude product. Combining the two prepared pedunculosides, and repeatedly recrystallizing with 10-100 times of 50-95% (volume content) ethanol to obtain a pure pedunculoside product (wherein the mass content of the pedunculoside is more than 98.0%).
In the application, the ovateleaf holly bark extract can be combined with other sleep-promoting medicines, such as other sleep-promoting medicines, so that the synergistic sleep-promoting effect can be obtained.
In the above application of the present application, the dosage of the above drugs can be obtained by reasonably adjusting and optimizing the dosage on the basis of the safe dosage for administration of the existing application of the two drugs. In particular sleep-promoting applications, the dosage administered may vary depending on the following factors: the disease state, age, sex, weight of the individual and the ability of the drug to elicit a desired response in the individual. For any particular subject, specific dosages may be adjusted over time according to the individual need and the professional judgment of the person to whom they are administered.
In a preferred embodiment of the application, the ilex rotundifolia thumb extract is ilex rotundifolia thumb total saponins, and the administration dosage of the ilex rotundifolia thumb total saponins is 100-200 mg/kg. In another preferred embodiment, the extract of cortex Ilicis Rotundae is pedunculoside, and the dose of pedunculoside is 50-100 mg/kg.
When the administration dose of the ilex rotundifolia total saponin is respectively 100mg/kg at the lowest dose and 200mg/kg at the highest dose, and the administration dose of the pedunculoside is respectively 50mg/kg at the lowest dose and 100mg/kg at the highest dose, the sleep-onset latency period caused by the suprathreshold dose or suprathreshold dose of the sodium pentobarbital can be shortened, and the sleep time of a mouse can be prolonged. If the dose of the ilex rotundifolia total saponins is less than 100mg/kg or the dose of the ilexoside is less than 50mg/kg, the ilex rotundifolia total saponins also has the effect of promoting sleep, but the effect of promoting sleep is slightly weak. When the administration dosage of the ilex rotunda thunb total saponin is higher than 200mg/kg or the administration dosage of the pedunculoside is higher than 100mg/kg, the ilex rotunda thunb total saponin also has the effect of promoting sleep, but potential administration risks can be generated.
In the above applications, the administration mode of the medicine containing the ilex rotunda thunb extract is selected according to the preparation form of the specific medicine. Preferably, the ilex rotundifolia extract is administered orally. And preferably, the pharmaceutical preparation is in the form of tablets, granules, capsules or oral liquid. The ovateleaf holly bark extract is prepared into the common preparation form, and the existing drug administration mode can be fully utilized.
The findings of the present application and their beneficial effects in improving and promoting sleep will be described below in conjunction with specific pharmacodynamic experiments.
Experiment-synergistic sodium pentobarbital sleep test
1.1 methods
The method comprises the steps of randomly grouping male and female halves of mice with the weight of 18-22 g according to the weight of the mice, wherein the mice are respectively a blank group, a diazepam 2mg/kg group, a pedunculoside low dose (50mg/kg) group, a high dose (100mg/kg) group, a rotunda officinalis total saponin low dose (100mg/kg) group and a high dose (200mg/kg) group.
On the experimental day, blank matrix, diazepam, pedunculoside and ovateleaf holly bark total saponin are respectively irrigated and taken once according to the dosage, and the administration volume is 0.2ml/10g body weight.
Pentobarbital sodium 35mg/kg (0.1ml/10g) is injected into abdominal cavity after administration for 40min, the disappearance and recovery of righting reflex of the mice after injection are observed, the time to fall asleep and the time to wake up are recorded, and the sleep latency and the sleep duration are calculated (if the righting reflex of the animals does not disappear within 1h, the sleep latency is recorded as 60min, and the sleep duration is recorded as 0 min). The calculation formulas of the sleep-in latency period and the sleep duration are respectively as follows:
the sleep-onset latency (min) is the disappearance of the righting reflex-the time of intraperitoneal injection of pentobarbital sodium.
Sleep duration (min) is wake-up time-righting reflex disappearance time.
Statistical analysis was then performed using the t-test to compare differences between groups. The statistical results are shown in Table 1.
Table 1: effect of pedunculoside on sleep time due to suprathreshold dose of sodium pentobarbital (
n＝16)
P <0.01 compared to placebo; p < 0.05.
1.2 results
As can be seen from table 1, the statistical results were significantly different for all four dose groups. When the administration doses of the ilex rotunda thunb total saponins are respectively 100mg/kg and 200mg/kg, and the administration doses of the pedunculoside are respectively 50mg/kg and 100mg/kg, the sleep-onset incubation period caused by suprathreshold dose of the pentobarbital sodium can be shortened, and the sleep time of a mouse can be prolonged.
Hypnotic test of experiment two synergistic sodium pentobarbital
2.1. Method of producing a composite material
Female mice were randomly divided into a blank group, a diazepam 2mg/kg group, a pedunculoside low dose (50mg/kg) group, a high dose (100mg/kg) group, a ilex rotunda total saponin low dose (100mg/kg) group, and a high dose (200mg/kg) group according to body weight.
On the experimental day, blank matrix, diazepam, pedunculoside and ovateleaf holly bark total saponin are respectively irrigated and taken once according to the dosage, and the administration volume is 0.2ml/10g body weight.
Pentobarbital sodium 24mg/kg (0.1ml/10g) was injected intraperitoneally after 40min of administration. And (3) observing the number of animals with disappearance of inversion and positive reflection within 1h after injection, recording the time for falling asleep and the time for waking up, and calculating the sleep-in latency and the sleep duration (if the animal does not disappear within 1h, the sleep-in latency is recorded as 60min, and the sleep duration is recorded as 0 min). The calculation formulas of the sleep-in latency period and the sleep duration are respectively as follows:
the sleep-onset latency (min) is the disappearance of the righting reflex-the time of intraperitoneal injection of pentobarbital sodium.
Sleep duration (min) is wake-up time-righting reflex disappearance time.
The number of animals with missing righting reflex was statistically analyzed by chi-square test, and the difference between groups was compared with the blank group; the sleep onset latency and sleep duration were statistically analyzed by t-test and differences between groups were compared. The statistical results are shown in Table 2.
TABLE 2 Effect of pedunculoside on hypnotic effect of sodium pentobarbital
P <0.001 compared to placebo; p < 0.01; p < 0.05.
2.2. Results
As can be seen from Table 2, the ilex rotundifolia total saponins can significantly promote sleep when the administration dosage is 100mg/kg and 200mg/kg respectively, and the administration dosage of the pedunculoside is 50mg/kg and 100mg/kg respectively, so that the number of sleeping animals is significantly increased. And the sleep-onset latency caused by the subthreshold dose of the sodium pentobarbital can be shortened, and the sleep time can be obviously prolonged.
From the above description, it can be seen that the above-described embodiments of the present invention achieve the following technical effects: the ilex rotundifolia is used as a medicinal plant with wide medical application, and the extract, particularly the total saponin extract, more preferably the pedunculoside in the total saponin extract can not only shorten the time of falling asleep, but also prolong the sleep time in the aspect of promoting sleep. Therefore, the application provides a new application of the ovateleaf holly bark extract in the aspect of promoting sleep, and provides a new choice for the preparation of the existing sleep-promoting medicine.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (3)
1. The application of pedunculoside as a unique active ingredient in preparing a sleep-promoting medicine is characterized in that the administration dosage of the pedunculoside is 50-100 mg/kg.
2. The use according to claim 1, wherein the medicament is administered orally.
3. The use according to claim 1, wherein the medicament is formulated in the form of a tablet, granule, capsule or oral liquid.
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| CN101982175B (en) * | 2006-09-19 | 2012-07-04 | 李超生 | Application of pedunculoside in preparing medicine for treating cerebral ischemia |
| CN101033245B (en) * | 2006-09-19 | 2011-02-16 | 李超生 | Preparation method and application of pedunculoside |
| CN104800491A (en) * | 2015-05-04 | 2015-07-29 | 何再亮 | Oral solution with superstrong function of improving human immunity |
| CN106074394A (en) * | 2016-07-01 | 2016-11-09 | 吉林省中医药科学院 | A kind of pharmaceutical composition preparation method improving insoluble drug Peltatin glucoside dissolution |
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| Inhibitory Activity of Chemical Constituents from;Guan-Shen Zhou;《Plant Medica》;20130313;第79卷(第8期);第687-692页 * |
| Syringin may exert sleep-potentiating effects through the NOS/NO pathway;Yue Cui;《Fundamental & Clinical Pharmacology》;20150415;第29卷(第2期);第178-184页 * |
| 铁冬青总皂苷心血管作用化学成分研究;王振辉;《中国优秀硕士学位论文全文数据库》;20111015(第10期);第E057-39页 * |
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