CN105796968A - Nerve-soothing granules for treating neurasthenia and insomnia and preparation method thereof - Google Patents
Nerve-soothing granules for treating neurasthenia and insomnia and preparation method thereof Download PDFInfo
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- CN105796968A CN105796968A CN201610244857.7A CN201610244857A CN105796968A CN 105796968 A CN105796968 A CN 105796968A CN 201610244857 A CN201610244857 A CN 201610244857A CN 105796968 A CN105796968 A CN 105796968A
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Classifications
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- A61K36/06—Fungi, e.g. yeasts
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- A61K36/074—Ganoderma
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- A—HUMAN NECESSITIES
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
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- A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
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Abstract
The invention belongs to the field of traditional Chinese medicine, and relates to nerve-soothing granules for neurasthenia, dizziness, insomnia, blood deficiency and dreaminess and a preparation method thereof. The traditional Chinese medicine granules are prepared from cortex albiziae, vine of multiflower knotweed, lucid ganoderma, Chinese dates, radix glycyrrhizae, glossy privet fruits, light wheat, a proper amount of excipient and a flow agent. The granules are remarkable in curative effect and good in stability, and the problems that existing nerve-soothing granules are poor in patient taking adaptability, insufficient in material utilization, long in extraction cycle and undefined in medicine effect are solved.
Description
Technical field
The invention belongs to the field of Chinese medicines, particularly relate to a kind of for neurasthenia, dizzy insomnia, Yening Granule agent of blood deficiency dreaminess and preparation method thereof.
Background technology
Insomnia is often to obtain a kind of disease that ortho sleep is feature, can behave as difficulty falling asleep, sleep and easily wake up, can not sleep again after waking up, morning wakes up too early, and time wakes up or can not fall asleep whole night when sleeping, and relates to the neurasthenia of modern medicine, combined external head injuries, fatigue syndrome, depression, schizophrenia, drug reaction and some physical disease, brain organic pathological changes etc..Reporting according to Recent study, its sickness rate has the trend of cumulative year after year, and this disease, as prevented and treated rightly not in time, can bring very big misery to patient.Though some Western medicine being currently used for treatment of insomnia patients has certain curative effect, but from basic treatment, and can not have certain side effect.The research and probe of insomnia be have accumulated abundant practical experience by motherland's medicine and pharmacology Chinese medicine, plays the advantage R. concomitans modern science and technology method of Chinese medicine, and exploitation Chinese medicine study has great learning value and social meaning.
Peaceful preparation was usually and made for raw material with Cortex Albiziae, Caulis Polygoni Multiflori, Ganoderma, Fructus Jujubae, Radix Glycyrrhizae, Fructus Ligustri Lucidi, Fructus Tritici Levis seven taste Chinese medicine existing night, major function is to calm the nerves to nourish heart, for neurasthenia, dizzy insomnia, the treatment of the sleep disorder that the factors such as blood deficiency dreaminess cause, its determined curative effect is reliable.
The preparation method of Yening Tangjiang recorded in " Chinese Pharmacopoeia " version one in 2000 is: after Fructus Tritici Levis adds water boil, in 80～90 DEG C of warm macerating 2 times, each 2 hours, merges warm macerating liquid；Ganoderma powder is broken into coarse powder, soaks a week by ethanol in proper amount, collects by filtration soak, reclaims ethanol standby；Its medicinal residues and Cortex Albiziae, Caulis Polygoni Multiflori, Fructus Jujubae, Radix Glycyrrhizae, Fructus Ligustri Lucidi boiling twice, each 3 hours, collecting decoction, filter, filtrate merges with the immersion of above-mentioned Fructus Tritici Levis and Ganoderma, stand, filters, and filtrate is concentrated into appropriate amount, adds certain adjuvant and makes syrup.This preparation method Shortcomings part: one, the extracting cycle of ganoderol extract is long, and concentration of alcohol and consumption indefinite；Two, the warm macerating process conditions of Fructus Tritici Levis, still there is indefinite part.
A kind of nano Medicine ' Yening ' and preparation method thereof disclosed in Chinese patent application CN01102093.8, after each taste medicine is first respectively prepared nano-scale particle by the method, make various preparation by the original prescription proportioning of " Chinese Pharmacopoeia " Yening Tangjiang again, but this application there is no definite drug effect and record.
The preparation method of peaceful medicine at a kind of night and solid preparation thereof disclosed in China Patent No. 200410041958.1, the consumption of water, when the warm macerating of Fructus Tritici Levis, limits by the method；During ganoderol extract, consumption and concentration to ethanol have also been made corresponding restriction；The independent spray drying of ganoderol extract, avoiding in concentration process that alcohol-soluble position and water soluble part are at extractum skewness, thus affecting drug quality, there is certain science, but also there is deficiency: 1. the warm macerating technique of Fructus Tritici Levis is big to the consumption of water, increases the time heated up；2., when ganoderol extracts, the concentration of ethanol is low, and alcohol extract content is not high；3. Fructus Tritici Levis is merged with (Ganoderma medicinal residues and all the other Chinese medicine extract) concentration and spray drying still has uncertain part；4. the powder body after spray drying there is uncertain part in the process making solid preparation；5. n-butanol extract is low.
And existing night, peaceful former dosage form was syrup, taste is bad, takes inconvenience, especially with respect to the crowd that those are sensitive to taste, is less useful for taking；Adding a large amount of sucrose is adjuvant, affects taking of diabetics；Dose is inaccurate, and in storage process vulnerable to pollution.
Summary of the invention
Present invention aim at Yening Granule agent that treatment neurasthenia's insomnia is provided and preparation method thereof.Meanwhile, in solution prior art, Yening Granule patient takes poor compliance, medical material utilizes insufficient, the indefinite problem of extracting cycle length, drug effect.
The Yening Granule agent for the treatment of neurasthenia's insomnia provided by the invention, described granule is made up of following component:
Cortex Albiziae 21 parts, Ganoderma 10 parts, Caulis Polygoni Multiflori 21 parts, 15 parts of Fructus Jujubae, Fructus Ligustri Lucidi 21 parts, 6 parts of Radix Glycyrrhizae, Fructus Tritici Levis 60 parts, excipient 5-10 part, fluidizer 0.5-2 part.
Wherein, described excipient is starch and microcrystalline Cellulose, and wherein said starch is preferably straight chain crystal starch,
The starch of described excipient and the mass ratio of microcrystalline Cellulose are 2: 1.
Further, fluidizer of the present invention is one or more in micropowder silica gel, Pulvis Talci and pregelatinized Starch.
It addition, the preparation method that present invention also offers a kind of Yening Granule agent treating neurasthenia's insomnia, comprise the following steps:
(1) weighing Cortex Albiziae 21 parts, Ganoderma 10 parts, Caulis Polygoni Multiflori 21 parts, 15 parts of Fructus Jujubae, Fructus Ligustri Lucidi 21 parts, 6 parts of Radix Glycyrrhizae, Fructus Tritici Levis 60 parts by weight, excipient 5-10 part, fluidizer 0.5-2 part is standby；
(2) Fructus Ligustri Lucidi of above-mentioned weight portion, Ganoderma are taken, add the water of 10-30 times of weight ratio, at pH value 4-6.5, the cellulase adding 1-5% weight ratio at temperature 40-60 DEG C, supersound extraction 1-2 hour, ultrasonic power controls at 180-260W, and the aqueous extract being filtrated to get is standby；
The percent by volume that above-mentioned Fructus Ligustri Lucidi after water extraction, Ganoderma residue add 3-8 times of weight is 45-60% ethanol extraction, extracts 3 times, each 1-3 hour, filters to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 30-60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(3) take the Caulis Polygoni Multiflori of above-mentioned weight portion, add the water of 3-10 times of weight ratio, at temperature 40-60 DEG C supersound extraction 1-3 hour, obtain aqueous extract；
It is 40-60% ethanol extraction by the percent by volume that above-mentioned Caulis Polygoni Multiflori residue after water extraction adds 3-8 times of weight, extracts 3 times, each 1-3 hour, filter to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 30-60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(4) take the Fructus Tritici Levis of above-mentioned weight portion, Radix Glycyrrhizae adds 8-10 times of soak by water 1.5-3 hour, decocts 3 times, filters, and merges decoction liquor, at 30-60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(5) take the Fructus Jujubae of above-mentioned weight portion, add 3-5 times of soak by water 1.5-3 hour, decoct 3 times, filter, merge decoction liquor, at 30-60 DEG C, decoction liquor is concentrated into relative density be 1.25-1.30 ask cream, prepare Fructus Jujubae aqueous extract clear paste；
(6) clear paste prepared by step (2), (3), (4), add excipient and fluidizer mixing, add the Fructus Jujubae aqueous extract clear paste that step (5) prepares, mixing, soft material processed, granulation, the dried granule that must dry, subpackage and get final product.
Further, the preferred following preparation technology of Yening Granule of the present invention:
(1) weighing Cortex Albiziae 21 parts, Ganoderma 10 parts, Caulis Polygoni Multiflori 21 parts, 15 parts of Fructus Jujubae, Fructus Ligustri Lucidi 21 parts, 6 parts of Radix Glycyrrhizae, Fructus Tritici Levis 60 parts by weight, excipient 5-10 part, fluidizer 0.5-2 part is standby；
(2) taking the Fructus Ligustri Lucidi of above-mentioned weight portion, Ganoderma, add the water of 30 times of weight ratios, add the cellulase of 2% weight ratio, supersound extraction 2 hours under pH value 6, temperature 50 C, ultrasonic power controls at 250W, and the aqueous extract being filtrated to get is standby；
The percent by volume that above-mentioned Fructus Ligustri Lucidi after water extraction, Ganoderma residue add 6 times of weight is 60% ethanol extraction, extracts 3 times, each 3 hours, filters to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 50 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(3) taking the Caulis Polygoni Multiflori of above-mentioned weight portion, add the water of 8 times of weight ratios, under temperature 50 C, supersound extraction 2 hours, obtain aqueous extract；
It is 60% ethanol extraction by the percent by volume that above-mentioned Caulis Polygoni Multiflori residue after water extraction adds 8 times of weight, extracts 3 times, each 2 hours, filter to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 50 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(4) take the Fructus Tritici Levis of above-mentioned weight portion, Radix Glycyrrhizae adds 10 times of soak by water 2.5 hours, decocts 3 times, filters, and merges decoction liquor, at 40 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(5) take the Fructus Jujubae of above-mentioned weight portion, add 3 times of soak by water 1.5 hours, decoct 3 times, filter, merge decoction liquor, at 40 DEG C, decoction liquor is concentrated into relative density be 1.25-1.30 ask cream, prepare Fructus Jujubae aqueous extract clear paste；
(6) clear paste prepared by step (2), (3), (4), add excipient and fluidizer mixing, add the Fructus Jujubae aqueous extract clear paste that step (5) prepares, mixing, soft material processed, granulation, the dried granule that must dry, subpackage and get final product.
Crude drug is carried out abundant extraction and application by the extraction process of the present invention, especially rare medicinal herbs Ganoderma is comprehensively extracted, improve the utilization rate of medical material, save cost, utilize Fructus Jujubae aqueous extract concentration clear paste as binding agent simultaneously, effectively utilize the mouthfeel that Fructus Jujubae itself is naturally sweet, improve patient's compliance to finished particle agent.
Compared with similar products, in its product, rheum emodin significantly improves, being increased to about 0.37mg/g by the 0.25mg/g of States Pharmacopoeia specifications, shown by pharmacological evaluation simultaneously, the granule that the present invention prepares is significantly better than, in treatment insomnia effect, prior art products such as including commercially available prod.
It is embodied as case
The present invention is further illustrated below by way of specific embodiment; but those skilled in the art should know specific embodiments of the invention and not limit the present invention in any way, and any equivalent replacement done on basis of the present invention each falls within protection scope of the present invention.
Comparative example 1
Prepare according to patent of invention 200410041958.1 embodiment 2--scheme 4 Yening Granule agent preparation method, obtain comparative example 1 Yening Granule.
Embodiment 1, the present invention treat the preparation of the Chinese medicine granules of neurasthenia's insomnia
(1) weighing Cortex Albiziae 21 parts, Ganoderma 10 parts, Caulis Polygoni Multiflori 21 parts, 15 parts of Fructus Jujubae, Fructus Ligustri Lucidi 21 parts, 6 parts of Radix Glycyrrhizae, Fructus Tritici Levis 60 parts by weight, starch 4 parts, microcrystalline Cellulose 2 parts, micropowder silica gel 1 part is standby；
(2) taking the Fructus Ligustri Lucidi of above-mentioned weight portion, Ganoderma, add the water of 30 times of weight ratios, add the cellulase of 2% weight ratio, supersound extraction 2 hours under pH value 6, temperature 50 C, ultrasonic power controls at 250W, and the aqueous extract being filtrated to get is standby；
The percent by volume that above-mentioned Fructus Ligustri Lucidi after water extraction, Ganoderma residue add 6 times of weight is 60% ethanol extraction, extracts 3 times, each 3 hours, filters to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 50 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(3) taking the Caulis Polygoni Multiflori of above-mentioned weight portion, add the water of 8 times of weight ratios, under temperature 50 C, supersound extraction 2 hours, obtain aqueous extract；
It is 60% ethanol extraction by the percent by volume that above-mentioned Caulis Polygoni Multiflori residue after water extraction adds 8 times of weight, extracts 3 times, each 2 hours, filter to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 50 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(4) take the Fructus Tritici Levis of above-mentioned weight portion, Radix Glycyrrhizae adds 10 times of soak by water 2.5 hours, decocts 3 times, filters, and merges decoction liquor, at 40 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(5) take the Fructus Jujubae of above-mentioned weight portion, add 3 times of soak by water 1.5 hours, decoct 3 times, filter, merge decoction liquor, at 40 DEG C, decoction liquor is concentrated into relative density be 1.25-1.30 ask cream, prepare Fructus Jujubae aqueous extract clear paste；
(6) clear paste prepared by step (2), (3), (4), add excipient and fluidizer mixing, add the Fructus Jujubae aqueous extract clear paste that step (5) prepares, mixing, soft material processed, granulation, the dried granule that must dry, subpackage and get final product.
Embodiment 2, the present invention treat the preparation of the Chinese medicine granules of neurasthenia's insomnia
(1) weighing Cortex Albiziae 21 parts, Ganoderma 10 parts, Caulis Polygoni Multiflori 21 parts, 15 parts of Fructus Jujubae, Fructus Ligustri Lucidi 21 parts, 6 parts of Radix Glycyrrhizae, Fructus Tritici Levis 60 parts by weight, starch 3 parts, microcrystalline Cellulose 1.5 parts, Pulvis Talci 1.5 parts is standby；
(2) taking the Fructus Ligustri Lucidi of above-mentioned weight portion, Ganoderma, add the water of 10 times of weight ratios, add the cellulase of 1% weight ratio, supersound extraction 1 hour at pH value 4, temperature 40 DEG C, ultrasonic power controls at 180W, and the aqueous extract being filtrated to get is standby；
The percent by volume that above-mentioned Fructus Ligustri Lucidi after water extraction, Ganoderma residue add 3 times of weight is 45% ethanol extraction, extracts 3 times, each 1 hour, filters to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 30 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(3) taking the Caulis Polygoni Multiflori of above-mentioned weight portion, add the water of 3 times of weight ratios, at temperature 40 DEG C, supersound extraction 1 hour, obtains aqueous extract；
It is 40% ethanol extraction by the percent by volume that above-mentioned Caulis Polygoni Multiflori residue after water extraction adds 3 times of weight, extracts 3 times, each 1 hour, filter to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 30 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(4) take the Fructus Tritici Levis of above-mentioned weight portion, Radix Glycyrrhizae adds 8 times of soak by water 1.5 hours, decocts 3 times, filters, and merges decoction liquor, at 30 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(5) take the Fructus Jujubae of above-mentioned weight portion, add 3 times of soak by water 1.5 hours, decoct 3 times, filter, merge decoction liquor, at 30 DEG C, decoction liquor is concentrated into relative density be 1.25-1.30 ask cream, prepare Fructus Jujubae aqueous extract clear paste；
(6) clear paste prepared by step (2), (3), (4), add excipient and fluidizer mixing, add the Fructus Jujubae aqueous extract clear paste that step (5) prepares, mixing, soft material processed, granulation, the dried granule that must dry, subpackage and get final product.
Embodiment 3, the present invention treat the preparation of the Chinese medicine granules of neurasthenia's insomnia
(1) weighing Cortex Albiziae 21 parts, Ganoderma 10 parts, Caulis Polygoni Multiflori 21 parts, 15 parts of Fructus Jujubae, Fructus Ligustri Lucidi 21 parts, 6 parts of Radix Glycyrrhizae, Fructus Tritici Levis 60 parts by weight, starch 5 parts, microcrystalline Cellulose 2.5 parts, pregelatinized Starch 2 parts is standby；
(2) taking the Fructus Ligustri Lucidi of above-mentioned weight portion, Ganoderma, add the water of 30 times of weight ratios, add the cellulase of 5% weight ratio, supersound extraction 2 hours under pH value 6.5, temperature 60 C, ultrasonic power controls at 260W, and the aqueous extract being filtrated to get is standby；
The percent by volume that above-mentioned Fructus Ligustri Lucidi after water extraction, Ganoderma residue add 8 times of weight is 60% ethanol extraction, extracts 3 times, each 3 hours, filters to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(3) taking the Caulis Polygoni Multiflori of above-mentioned weight portion, add the water of 10 times of weight ratios, under temperature 60 C, supersound extraction 3 hours, obtain aqueous extract；
It is 60% ethanol extraction by the percent by volume that above-mentioned Caulis Polygoni Multiflori residue after water extraction adds 8 times of weight, extracts 3 times, each 3 hours, filter to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(4) take the Fructus Tritici Levis of above-mentioned weight portion, Radix Glycyrrhizae adds 10 times of soak by water 3 hours, decocts 3 times, filters, and merges decoction liquor, at 60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(5) take the Fructus Jujubae of above-mentioned weight portion, add 5 times of soak by water 3 hours, decoct 3 times, filter, merge decoction liquor, at 60 DEG C, decoction liquor is concentrated into relative density be 1.25-1.30 ask cream, prepare Fructus Jujubae aqueous extract clear paste；
(6) clear paste prepared by step (2), (3), (4), add excipient and fluidizer mixing, add the Fructus Jujubae aqueous extract clear paste that step (5) prepares, mixing, soft material processed, granulation, the dried granule that must dry, subpackage and get final product.
Embodiment 4, Chinese medicine granules of the present invention component content determination test
1, test material
1.1, emodin content measures:
null(1) need testing solution: accurate amount weighs inventive embodiments 1、Embodiment 2、The Chinese medicine granules of embodiment 3 preparation、Commercially available Yening Granule (Lishizhen Medicine Group Co., Ltd.'s production)、The each 0.4g of comparative example 1 granule，Put respectively in 50ml conical flask，Add water 20ml to dissolve，It is slowly added dropwise sulphuric acid 1ml，Shake up，Ultrasonic 5min，Add chloroform 20ml，Heating in water bath backflow 30min，Divide and take chloroform layer，Add chloroform 20ml again，Continue to be heated to reflux 30min，Divide and add chloroform 20ml again after taking chloroform layer，Continue to be heated to reflux 20min，So repeatedly extract to chloroform layer closely colourless，Combined chloroform liquid，Use a small amount of water washing，Divide and take chloroform layer，Volatilize，Residue methanol washs，Cleaning mixture moves in 10ml measuring bottle，Methanol adds to scale，Shake up，Stand，Filter，Take subsequent filtrate，Obtain.
(2) reference substance solution: precision weighs rheum emodin reference substance 2mg and is placed in 25ml measuring bottle, dissolves with methanol and is diluted to scale, shaking up, precision measures rheum emodin solution 1ml and puts in 25ml measuring bottle, adds methanol to scale, shakes up, to obtain final product.
2, test method
Adopting and measure according to high performance liquid chromatography (Chinese Pharmacopoeia one annex VID of version in 2010), precision draws reference substance solution and each 20 μ L of need testing solution respectively, injects chromatograph of liquid, measures, to obtain final product.
3, result of the test
5 groups of samples are carried out assay, and result is as shown in table 1 (n=3).
The component content determination test result of table 1 Chinese medicine granules of the present invention
As shown in Table 1, Yening Granule emodin content prepared by embodiment of the present invention 1-3 prepares gained Yening Granule apparently higher than commercially available and art methods, meets the States Pharmacopoeia specifications requirement more than 0.25mg/g simultaneously.
Embodiment 6, Chinese medicine granules of the present invention stability test
Accelerated test and long term test is made according to the Chinese medicine granules of the preparation of the embodiment of the present invention 1.
1, test material
(1) sample: by the Chinese medicine granules sample of embodiments of the invention 1 preparation, specification is 10g/ bag.
(2) instrument: stability experiment supports case, horizontal laminar flow clean work station etc..
2, test method
(1) accelerated stability test: take above-mentioned 100 bags of products, temperature 40 DEG C ± 2 DEG C, places when relative humidity 75% ± 5%, respectively testing 1st month period, 2 months 3 months, sampling at 6 the end of month is observed.
(2) long-term stable experiment: take above-mentioned 100 bags of products, at room temperature preserve, observes by " new Chinese medicine stability test guideline ".
3, test index
Observe the outward appearance of granule, melting, assay, Micro biological Tests.
4, result of the test
The accelerated stability test result of Chinese medicine granules of the present invention is as shown in table 2, and the long-term stable experiment result of Chinese medicine granules of the present invention is as shown in table 3.
The accelerated stability test result of table 2 Chinese medicine granules of the present invention
The long-term stable experiment result of table 3 Chinese medicine granules of the present invention
The Chinese medicine granules of the embodiment of the present invention 1 preparation is placed half a year when accelerated test and under room temperature condition, draw from 0 month, January, February, March, acceleration in June and long-term observed result, each investigates project all less than abnormal, all meet quality criteria requirements, illustrate that the granule stability of the present invention is high, be conducive to the preservation of this Chinese medicine granules.
Embodiment 7, granule excipient kind select test
Taking the Chinese medicine granules of the 10 parts of embodiment of the present invention 1 preparations respectively, put in tray, every two parts is a Duplicate Samples, is exposed to 24h under relative humidity 70% damp condition, observes the outward appearance of granule.Result of the test is as shown in table 4.
The test that the kind of table 4 granule excipient selects
| Excipient type | Outward appearance |
| Straight chain crystal starch: microcrystalline Cellulose (mass ratio 1: 1) | Color and luster is consistent, a small amount of caking phenomenon, graininess occurs |
| Straight chain crystal starch: microcrystalline Cellulose (mass ratio 2: 1) | Color and luster is consistent, without caking phenomenon, graininess |
| Straight chain crystal starch: microcrystalline Cellulose (mass ratio: 3: 1) | Color and luster is consistent, a small amount of caking phenomenon, graininess occurs |
| Straight chain crystal starch | Color and luster is consistent, more caking phenomenon occurs, a small amount of powdery occurs |
| Microcrystalline Cellulose | Color and luster is consistent, more caking phenomenon, graininess occurs |
Adopt straight chain crystal starch as can be seen from Table 4: microcrystalline Cellulose (mass ratio 2: 1) is excipient, it is possible to the moisture resistance being greatly improved granule and the adhesion increased between powder, effectively prevent granule powdery phenomenon.
Embodiment 8, granule pharmacological research of the present invention.
Test medicine: medicine of the present invention, hereinafter referred to as Yening Granule, is prepared by embodiment 1-3 preparation technology.
Animal: Kunming mouse, closed colony, body weight 20-25g, male and female are regardless of.
Test method selects:
Prescription feature according to clinical therapeutic efficacy and the present invention, for verifying clinical efficacy, has carried out following selection with regard to its main pharmacodynamics science study method:
1, adopt walking time, lift double; two forelimb method and ambulatory activity count method, in order to observe the sedation of medicine.
2, the medicine synergism to the pentobarbital sodium length of one's sleep is observed.
3, the medicine sleep number to pentobarbital sodium sub-threshold dose animal is observed.
Selective dose: owing to LD50 fails to measure, therefore with reference to clinical medicine dose, press the ratio calculation of human body and animal body surface area equivalent dosage, select the high, medium and low Three doses of mice respectively 21.2g crude drug/kg, 10.6g crude drug/kg, 5.2g crude drug/kg (respectively 8 times of dose,equivalent, 4 times, 2 times), the equal gastric infusion of animal (ig).
Medication: Yening Granule clinic is oral, the equal gastric infusion of animal experiment, route of administration is consistent with clinical application, and this medicine is administered 3 times every day, continuous 5 days.
Experimental control selects:
Blank: number of animals, body weight, sex are with administration group, by administration high dose to same volume distilled water.
Positive control: chlorpromazine HCL tablet, clinical adult 50mg/ days, press human body to calculate with animal body surface area equivalent dose ratio, its dose,equivalent is 6.5mg/kg, and dose,equivalent 2 times is selected in test, and dosage is 13.0mg/kg, used time grinds, it is made into desired concn with distilled water to stir administration, lot number: 131209, Beijing benefit people's Pharmaceutical；Aspirin Enteric-coated Tablets, this product, containing aspirin 0.3g, faces the used time except sugar-coat grinding, selective dose 0.6g/kg, lot number 890801, and Jilin pharmaceutical factory produces.
Model comparison: strychnine powder, is made into 0.02% concentration with normal saline, and selecting to cause frightened dosage is 1.2mg/kg, and by animal subcutaneous administration, lot number: 1310791, Germany LIC company produces.
Main experimental step and result
One, sedation
1, on mice walking time and the impact lifting double; two forelimb
nullExperimental selection female mice 50，It is randomly divided into five groups，Every treated animal 10，1-3 is that Yening Granule is high、In、Low dose group，Dosage respectively 21.2g crude drug/kg、10.6g crude drug/kg、5.3g crude drug/kg，4 groups is chlorpromazine hydrochloride dosage 0.013g/kg，Comparative example group administration comparative example 1 prepares Yening Granule agent，The equal gastric infusion of animal，Every day 3 times，Continuous 5 days，30min after last is administered，Each group of mice is put into (15cm × 25cm × 20cm rectangle the case made with colourless lucite in active box，Wood flour bedding and padding are put in bottom) adapt to 5min，Record takes after Activity value in 2min (with 2min walking time and lift double; two forelimb and upwards praise number of times for index) record administration respectively 30、60、90、120min active situation，Result is in Table 5、6.
The impact on mice walking time of table 5 Yening Granule
Compare with matched group***P < 0.001,**P < 0.01,*P < 0.05.
Mice forelimb is upwards praised the impact of number of times by table 6 Yening Granule
Compare with matched group***P < 0.001,**P < 0.01,*P < 0.05.
2, the impact on mice autonomic activities
Take mice 50, male and female half and half, body weight 20-24g, is randomly divided into five groups by group shown in table 5 and dosage, every treated animal 10, the equal gastric infusion of mice, continuous 5 days, 1h after last is administered, puts in XZC-1 type toy autonomic activities analyzer respectively by mice, observing and record mice autonomic activities number of times in 10min, result is in Table 7.
The impact on mice autonomic activities of table 7 Yening Granule
Compare with matched group**P < 0.01,*P < 0.05.
Two, syngignoscism
1, the impact on pentobarbital sodium mouse sleep time
Select body weight 18-22g mice 50, male and female half and half, by rank and dosage shown in table 7, are randomly divided into five groups, every treated animal 10, the equal gastric infusion of animal, every day 3 times, for three days on end, it is administered 1hr in last, by every Mus lumbar injection threshold dose Nembutal sodium solution 50mg/kg, with mice righting reflex loss for time for falling asleep, record each group of mice from righting reflex loss to the sleep time of recovery time.Result is in Table 8.
The impact on the mice pentobarbital sodium length of one's sleep of table 8 Yening Granule
Compare with matched group***P < 0.001,**P < 0.01,*P < 0.05.
2, the impact on pentobarbital sodium sub-threshold dose mice sleep number
Selecting body weight 18-22g mice 50, male and female half and half, by group and dosage shown in table 8, it is randomly divided into five groups, every treated animal 10, the equal gastric infusion of animal, every day 3 times, for three days on end, 1h after last is administered, by lumbar injection (sub-threshold dose that trial test selects) Nembutal sodium solution 26mg/kg, with mice more than righting reflex loss 1min for sleep index, observing mice sleep number in 15min, test adopts X2 value inspection administration group and the matched group significance of difference.Result is in Table 9
The impact on mice sleep number of table 9 Yening Granule
Table 5-9 test result indicate that, Yening Granule 21.2g crude drug/kg, 10.6g crude drug/kg, 5.3g crude drug/kg tri-kinds various dose is to animal gastric infusion, continuous 5 days, can obviously reduce mice walking time and double, two forelimb praises number of times, in experiment, the activity of perusal mice significantly reduces, wherein high dose sedation effect is the most obvious, but not as positive drug chlorpromazine, confirmed by two experiments, this product has certain sedation, test simultaneously and also observe syngignoscism, under shown dosage, Yening Granule can be obviously prolonged the length of one's sleep of pentobarbital sodium, and pentobarbital sodium sub-threshold dose animal sleep number can be increased, prompting this product has certain syngignoscism, from this experiment, this product calmness is likely to relevant with central nerve inhibition with syngignoscism.Simultaneously compared with comparative example, the Yening Granule that preparation method of the present invention prepares, emodin content is significantly higher than comparative example, shown by pharmacological evaluation, in treatment insomnia effect Yening Granule of the present invention significantly due to existent technique in Yening Granule.
Animal acute toxicity test result of the present invention:
Yening Granule, 2.04g crude drug/g, to the disposable gastric infusion 0.4g/10g of mice, to observe 7 days, none Mus is dead, therefore LD50 fails to measure.Animal maximum tolerated dose measures, result is administered this product to mouse stomach, every Mus gastric infusion 1.8g on the 1st, except administration animal on the same day has quiet phenomenon, more than show no obvious abnormalities situation, therefore recording mouse stomach, to be administered this product maximum tolerated dose be 183.6g crude drug/kg, is equivalent to 633 times of clinical application amount.
Long-term toxicity test for animals result of the present invention:
Yening Granule 29.44g crude drug/kg, 22.08g crude drug/kg, 14.72g crude drug/kg (is respectively equivalent to 101.6 times of clinical application, 76.1 again, 50.8 again) three dosage are to rat oral gavage, continuous 4 weeks, result shows, rat is seen through place and checks, routine blood test (RBC, WBC, Hb, BPC, leaflet, lymph), routine urinalysis (urine protein, RBC/ × 400, WBC/ × 400) and the every biochemical indicator (ALT of blood, BUN, CRE, T-CHO, GLU, TP) measure and compare the equal > 0.05 of P with matched group, histopathologic examination is showed no organs and tissues abnormal change, confirm that this product long-term taking has no side effect.
Conclusion
Yening Granule, under shown dosage, has calmness, hypnosis, many-sided pharmacological action such as calm the nerves, and these effects are consistent with clinical therapeutic efficacy, and pointing out this product is good calmness, hypnotic drug, it is adaptable to the treatment of insomnia.Toxicological experiment shows granule safety of the present invention, is suitable for Clinical practice.
Claims (7)
1. the preparation method of the Yening Granule agent treating neurasthenia's insomnia, it is characterized in that raw material consists of: Cortex Albiziae 21 parts, Ganoderma 10 parts, Caulis Polygoni Multiflori 21 parts, 15 parts of Fructus Jujubae, Fructus Ligustri Lucidi 21 parts, 6 parts of Radix Glycyrrhizae, Fructus Tritici Levis 60 parts, excipient 5-10 part, fluidizer 0.5-2 part, be prepared from by following step:
(1) Cortex Albiziae, Ganoderma, Caulis Polygoni Multiflori, Fructus Jujubae, Fructus Ligustri Lucidi, Radix Glycyrrhizae, Fructus Tritici Levis are weighed by weight standby；
(2) Fructus Ligustri Lucidi of above-mentioned weight portion, Ganoderma are taken, add the water of 10-30 times of weight ratio, at pH value 4-6.5, the cellulase adding 1-5% weight ratio at temperature 40-60 DEG C, supersound extraction 1-2 hour, ultrasonic power controls at 180-260W, and the aqueous extract being filtrated to get is standby；
The percent by volume that above-mentioned Fructus Ligustri Lucidi after water extraction, Ganoderma residue add 3-8 times of weight is 45-60% ethanol extraction, extracts 3 times, each 1-3 hour, filters to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 30-60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(3) take the Caulis Polygoni Multiflori of above-mentioned weight portion, add the water of 3-10 times of weight ratio, at temperature 40-60 DEG C supersound extraction 1-3 hour, obtain aqueous extract；
It is 40-60% ethanol extraction by the percent by volume that above-mentioned Caulis Polygoni Multiflori residue after water extraction adds 3-8 times of weight, extracts 3 times, each 1-3 hour, filter to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(4) take the Fructus Tritici Levis of above-mentioned weight portion, Radix Glycyrrhizae adds 8-10 times of soak by water 1.5-3 hour, decocts 3 times, filters, and merges decoction liquor, at 60 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(5) take the Fructus Jujubae of above-mentioned weight portion, add 3-5 times of soak by water 1.5-3 hour, decoct 3 times, filter, merge decoction liquor, decoction liquor is concentrated into relative density be 1.25-1.30 ask cream, prepare Fructus Jujubae aqueous extract clear paste；
(6) clear paste prepared by step (2), (3), (4), add excipient and fluidizer mixing, add the Fructus Jujubae aqueous extract clear paste that step (5) prepares, mixing, soft material processed, granulation, the dried granule that must dry, subpackage and get final product.
2. preparation method according to claim 1, it is characterised in that described excipient is the mass ratio of starch and microcrystalline Cellulose, starch and microcrystalline Cellulose is 2: 1, and wherein said starch is preferably straight chain crystal starch.
3. preparation method according to claim 1, it is characterised in that described fluidizer is one or more in micropowder silica gel, Pulvis Talci and pregelatinized Starch.
4. the preparation method of the Yening Granule agent treating neurasthenia's insomnia, it is characterized in that raw material consists of: Cortex Albiziae 21 parts, Ganoderma 10 parts, Caulis Polygoni Multiflori 21 parts, 15 parts of Fructus Jujubae, Fructus Ligustri Lucidi 21 parts, 6 parts of Radix Glycyrrhizae, Fructus Tritici Levis 60 parts, excipient 5-10 part, fluidizer 0.5-2 part, is prepared from by following step:
(1) Cortex Albiziae, Ganoderma, Caulis Polygoni Multiflori, Fructus Jujubae, Fructus Ligustri Lucidi, Radix Glycyrrhizae, Fructus Tritici Levis are weighed by weight standby；
(2) taking the Fructus Ligustri Lucidi of above-mentioned weight portion, Ganoderma, add the water of 30 times of weight ratios, add the cellulase of 2% weight ratio, supersound extraction 2 hours under pH value 6, temperature 50 C, ultrasonic power controls at 250W, and the aqueous extract being filtrated to get is standby；
The percent by volume that above-mentioned Fructus Ligustri Lucidi after water extraction, Ganoderma residue add 6 times of weight is 60% ethanol extraction, extracts 3 times, each 3 hours, filters to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 50 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(3) taking the Caulis Polygoni Multiflori of above-mentioned weight portion, add the water of 8 times of weight ratios, under temperature 50 C, supersound extraction 2 hours, obtain aqueous extract；
It is 60% ethanol extraction by the percent by volume that above-mentioned Caulis Polygoni Multiflori residue after water extraction adds 8 times of weight, extracts 3 times, each 2 hours, filter to obtain alcohol extract；
Merge above-mentioned aqueous extract and alcohol extract, at 50 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(4) take the Fructus Tritici Levis of above-mentioned weight portion, Radix Glycyrrhizae adds 10 times of soak by water 2.5 hours, decocts 3 times, filters, and merges decoction liquor, at 40 DEG C, decoction liquor is concentrated into the clear paste that relative density is 1.25-1.30 standby；
(5) take the Fructus Jujubae of above-mentioned weight portion, add 3 times of soak by water 1.5 hours, decoct 3 times, filter, merge decoction liquor, at 40 DEG C, decoction liquor is concentrated into relative density be 1.25-1.30 ask cream, prepare Fructus Jujubae aqueous extract clear paste；
(6) clear paste prepared by step (2), (3), (4), add excipient and fluidizer mixing, add the Fructus Jujubae aqueous extract clear paste that step (5) prepares, mixing, soft material processed, granulation, the dried granule that must dry, subpackage and get final product.
5. preparation method according to claim 4, it is characterised in that described excipient is the mass ratio of starch and microcrystalline Cellulose, starch and microcrystalline Cellulose is 2: 1, and wherein said starch is preferably straight chain crystal starch.
6. preparation method according to claim 4, it is characterised in that described fluidizer is one or more in micropowder silica gel, Pulvis Talci and pregelatinized Starch.
7. the Yening Granule prepared according to claim 1-6 any one preparation method.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108888722A (en) * | 2018-08-13 | 2018-11-27 | 河南中医药大学 | A kind of integration of drinking and medicinal herbs Chinese medicine jujube with treatment insomnia of calming the nerves is soothed the spirit particle |
| CN114306256A (en) * | 2022-01-13 | 2022-04-12 | 山东新时代药业有限公司 | Isosorbide mononitrate tablet and preparation process thereof |
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| CN1615962A (en) * | 2004-09-08 | 2005-05-18 | 丁青龙 | Method for preparing night rest medicine and its solid preparation |
| CN101129633A (en) * | 2007-09-19 | 2008-02-27 | 吉林省辉南天宇药业股份有限公司 | Medicine for neurasthenia and its preparation |
| CN103735905A (en) * | 2013-12-30 | 2014-04-23 | 海南葫芦娃制药有限公司 | Yening capsule and preparation method thereof |
| CN104666832A (en) * | 2015-03-20 | 2015-06-03 | 广州一品红制药有限公司 | Traditional Chinese medicinal granule for treating cold and repeated cold, and preparation method for traditional Chinese medicinal granule |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1615962A (en) * | 2004-09-08 | 2005-05-18 | 丁青龙 | Method for preparing night rest medicine and its solid preparation |
| CN101129633A (en) * | 2007-09-19 | 2008-02-27 | 吉林省辉南天宇药业股份有限公司 | Medicine for neurasthenia and its preparation |
| CN103735905A (en) * | 2013-12-30 | 2014-04-23 | 海南葫芦娃制药有限公司 | Yening capsule and preparation method thereof |
| CN104666832A (en) * | 2015-03-20 | 2015-06-03 | 广州一品红制药有限公司 | Traditional Chinese medicinal granule for treating cold and repeated cold, and preparation method for traditional Chinese medicinal granule |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108888722A (en) * | 2018-08-13 | 2018-11-27 | 河南中医药大学 | A kind of integration of drinking and medicinal herbs Chinese medicine jujube with treatment insomnia of calming the nerves is soothed the spirit particle |
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Application publication date: 20160727 |