CN106138039A - A kind of epiphysin preparation improving sleep and preparation method thereof - Google Patents
A kind of epiphysin preparation improving sleep and preparation method thereof Download PDFInfo
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- CN106138039A CN106138039A CN201610508434.1A CN201610508434A CN106138039A CN 106138039 A CN106138039 A CN 106138039A CN 201610508434 A CN201610508434 A CN 201610508434A CN 106138039 A CN106138039 A CN 106138039A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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Abstract
The invention discloses a kind of epiphysin preparation improving sleep and preparation method thereof.Including the raw material of following weight portion, epiphysin 1~3 part, starch 130~170 parts, white granulated sugar 100~156 parts, 70~144 parts of dextrin, talcum powder 2~6 parts, magnesium stearate 2~6 parts and sodium carboxymethylcellulose 0.2~2 part.The epiphysin preparation improving sleep of the present invention has that safety non-toxic, good mouthfeel, dose be few and the feature of no dependence.Test shows, the epiphysin preparation of the present invention can significantly extend yellow Jackets lengths of one's sleep, collaborative yellow Jackets sub-threshold dose syngignoscism and shorten barbital sodium Sleep latency, has the function significantly improving sleep.
Description
Technical field:
The invention belongs to technical field of health care products, be specifically related to a kind of epiphysin preparation improving sleep and preparation thereof
Method.
Background technology:
In all one's life of people, the time of about 1/3rd is had to spend in sleep, the quality of sleep and healthy breath manner of breathing
Close.Medical research shows, insomnia once in a while can cause second day tired and exercise not harmony, and chronic insomnia then can bring notice not
Can concentrate, there is obstacle in memory and the consequence such as unable to do what one wishes that works, and meanwhile, not having enough sleep to make body immunity decline, disease-resistant
Reduce with rehabilitation ability, usually can easily send out flu, and have the possibility increasing the weight of other diseases or inducing original disease.
The product variety improving sleep in the market is a lot, and wherein most is all Chinese patent drug composition, with epiphysin is
Raw material of less types, formulation has oral liquid, capsule, medicinal tea, tablet etc., and mouthfeel is poor.
Epiphysin is the hormone of a kind of human endogenous's property, the sleep of chief leading cadre's body, clear-headed cycle.Pineal body secretion is taken off
Melanocyte, when the evening draws on, pineal body discharges epiphysin, makes temperature decline, and heart rates slows down, and brain is transferred to by excitement and pressing down
System, enters sleep state.As dawn gradually reveals, the secretory volume of epiphysin can be gradually lowered, and daytime, the secretory volume of epiphysin was not enough
The 50% of night, here it is the rule of epiphysin daily rhythmicity change.
Content of the invention:
First purpose of the present invention is to provide that a kind of safety non-toxic, good mouthfeel, dose be few, the improvement of no dependence
Epiphysin preparation of sleep and preparation method thereof.
A kind of epiphysin preparation improving sleep, including the raw material of following weight portion, epiphysin 1~3 part, starch 130~
170 parts, white granulated sugar 100~156 parts, 70~144 parts of dextrin, talcum powder 2~6 parts, magnesium stearate 2~6 parts and carboxymethyl cellulose
0.2~2 part of sodium of element.
Preferably, including the raw material of following weight portion, epiphysin 2~3 parts, starch 150~170 parts, white granulated sugar 120~150
Part, 90~130 parts of dextrin, talcum powder 4~5 parts, magnesium stearate 4~6 parts and sodium carboxymethylcellulose 0.5~1 part.
Preferably, including the raw material of following weight portion, epiphysin 3 parts, starch 150 parts, white granulated sugar 128 parts, 110 parts of dextrin,
Talcum powder 4 parts, magnesium stearate 4 parts and sodium carboxymethylcellulose 1 part.
Preferably, by weight, film coating agent 8~16 parts is also included.
Described film coating agent, including the raw material of following weight portion: Hydroxypropyl methylcellulose 3.6 parts, talcum powder 3.6 parts,
Titanium dioxide 0.8 part, 1,2-PD 1.3 parts and Tween-80 1.3 parts.
Second object of the present invention is to provide the preparation method of a kind of above-mentioned epiphysin preparation improving sleep, including
Following steps: a) by required weight portion in the above-mentioned epiphysin preparation improving sleep weigh respectively epiphysin, starch, dextrin,
White granulated sugar, talcum powder and magnesium stearate sieve after pulverizing;B) sodium carboxymethylcellulose of required weight portion is dissolved in the water
Sodium carboxymethylcellulose is starched;C) mixed material is obtained after epiphysin, starch, dextrin and white granulated sugar being mixed;D) by mixture
Material mixes with sodium carboxymethylcellulose slurry, and through pelletizing, grain dry, whole obtains dry particle;E) by dry particle and talcum powder, hard
Fatty acid magnesium obtains, after mixing, the material always mixing, and obtains improving the epiphysin preparation of sleep through compressing tablet, coating.
Preferably, described sodium carboxymethylcellulose slurry is starched for the sodium carboxymethylcellulose that mass fraction is 2%.
Described epiphysin, starch, dextrin and white granulated sugar are mixed after mixed material is by equal increments mixing
Epiphysin and starch are first mixed by method, obtain mixed material with dextrin, white granulated sugar after then mixing.
The epiphysin preparation improving sleep of the present invention has that safety non-toxic, good mouthfeel, dose be few and no dependence
Feature.Test shows, the epiphysin preparation of the present invention can significantly extend yellow Jackets lengths of one's sleep, collaborative amobarbital
Sodium sub-threshold dose syngignoscism and shortening barbital sodium Sleep latency, have the function significantly improving sleep.
Brief description:
Fig. 1 is the preparation flow figure of the epiphysin preparation improving sleep of the present invention.
Detailed description of the invention:
Following example are to further illustrate the present invention, rather than limitation of the present invention.
Embodiment 1: improve the preparation of the epiphysin preparation A of sleep
The epiphysin preparation improving sleep of the present embodiment, including following raw material: epiphysin 3kg, starch 150kg, white sand
Sugar 128kg, dextrin 110kg, talcum powder 4kg, magnesium stearate 4kg, sodium carboxymethylcellulose 1kg and film coating agent 10.6kg.
Improve the preparation method (as shown in Figure 1) of the epiphysin preparation A of sleep, comprise the following steps:
Step 1) weigh after the epiphysin of formula ratio, starch, white granulated sugar and dextrin are pulverized and cross 100 mesh sieves;Weigh formula ratio
Talcum powder and magnesium stearate pulverize after cross 40 mesh sieves, standby;
Step 2) sodium carboxymethylcellulose of formula ratio is joined in purified water, it is heated to 50-60 DEG C, stirring is to carboxylic first
Base sodium cellulosate is completely dissolved, and becomes clear transparent solutions, makes the sodium carboxymethylcellulose slurry that mass fraction is 2%, standby;
Step 3) press equal increments mixing method, first epiphysin and starch are mixed, then mix with dextrin, white granulated sugar
Close, obtain mixed material;
Step 4) the sodium carboxymethylcellulose slurry that mixed material and mass fraction are 2% is mixed, cross 16 mesh sieve systems
Grain, obtains wet granular, standby;
Step 5) use chamber dryer to be dried wet granular, baking temperature is 55-50 DEG C, and drying time is 1-3
Hour, be dried after 15min and stir dish endoparticle, make particles by heat uniform, obtain dry particle, the moisture of dry particle control≤
5%;
Step 6) dry particle is crossed 16 mesh sieves carry out whole grain;
Step 7) the dry particle after whole grain and talcum powder, magnesium stearate always to be mixed, incorporation time is 15-30 minute,
Obtain total mixed material;
Step 8) compressing tablet is carried out to total mixed material, obtain element piece;
Step 9) ethanol that the film coating agent volume fraction of formula ratio is 70% is made mass fraction is 9.5-
The film coating slurry of 12%, puts into element piece in seed-coating machine, is subsequently adding film coating slurry, makes element piece wrap film-coating, obtains
Improve the epiphysin preparation A of sleep.
Above-mentioned film coating agent, including the raw material of following weight portion: Hydroxypropyl methylcellulose 3.6 parts, talcum powder 3.6 parts,
Titanium dioxide 0.8 part, 1,2-PD 1.3 parts and Tween-80 1.3 parts.
Embodiment 2: improve the preparation of the epiphysin preparation B of sleep
The epiphysin preparation improving sleep of the present embodiment, including following raw material: epiphysin 1kg, starch 130kg, white sand
Sugar 120kg, dextrin 144kg, talcum powder 5kg, magnesium stearate 2kg, sodium carboxymethylcellulose 0.5kg and film coating agent 8kg.
The preparation method of the epiphysin preparation B improving sleep is identical with the preparation method of embodiment 1.
The formula of the film coating agent of the present embodiment is identical with the formula of embodiment 1.
Embodiment 3: improve the preparation of the epiphysin formulation C of sleep
The epiphysin preparation improving sleep of the present embodiment, including following raw material: epiphysin 2kg, starch 170kg, white sand
Sugar 150kg, dextrin 70kg, talcum powder 2kg, magnesium stearate 4kg, sodium carboxymethylcellulose 2kg and film coating agent 12kg.
The preparation method of the epiphysin formulation C improving sleep is identical with the preparation method of embodiment 1.
The formula of the film coating agent of the present embodiment is identical with the formula of embodiment 1.
Embodiment 4: improve the preparation of the epiphysin preparation D of sleep
The epiphysin preparation improving sleep of the present embodiment, including following raw material: epiphysin 2kg, starch 130kg, white sand
Sugar 100kg, dextrin 70kg, talcum powder 6kg, magnesium stearate 6kg, sodium carboxymethylcellulose 0.2kg and film coating agent 8.8kg.
The preparation method of the epiphysin preparation D improving sleep is identical with the preparation method of embodiment 1.
The formula of the film coating agent of the present embodiment is identical with the formula of embodiment 1.
Embodiment 5: improve the preparation of the epiphysin preparation E of sleep
The epiphysin preparation improving sleep of the present embodiment, including following raw material: epiphysin 3kg, starch 130kg, white sand
Sugar 156kg, dextrin 90kg, talcum powder 4kg, magnesium stearate 4kg, sodium carboxymethylcellulose 2kg and film coating agent 16kg.
The preparation method of the epiphysin preparation E improving sleep is identical with the preparation method of embodiment 1.
The formula of the film coating agent of the present embodiment is identical with the formula of embodiment 1.
Embodiment 6: epiphysin preparation toxicological assessment is tested
Toxicological safety is carried out to the epiphysin preparation A~E improving sleep of embodiments of the invention 1~embodiment 5
Evaluation test.Check conclusion: 1. acute oral toxicity test: give to change with maximum dosage-feeding (dosage is 30000mg/kg BW)
After the epiphysin preparation of kind sleep, having no that mouse has poisoning symptom, without animal dead, animal, gross examination of skeletal muscle are dissected in off-test
No abnormality seen, belongs to non-poisonous material.2. genetic toxicity test: three genetic toxicity tests (Ames, mouse marrow cell micro nuclear test,
Mouse inbred strain) result is feminine gender.3.30 days feeding trials: with the 667th, the 500th, 333mg/kg BW (be respectively equivalent to
Human body recommends consumption the 100th, the 75th, 50 times) the epiphysin preparation improving sleep of 3 dosage is continuously to rat oral gavage 30 days, experiment
Growing of period animal is good, and the weight of animals of each dosage group, gain in weight, food-intake, food utilization, routine blood test refer to
Mark, blood biochemistry index, organ weights and internal organs/body weight ratio compare with control group, difference that there are no significant (P > 0.05);Substantially
Anatomic observation and histopathological examination have no the abnormal change relevant with the epiphysin preparation improving sleep.Prompting has no that this changes
The epiphysin preparation of kind sleep feeds the toxic effect to rat in 30 days.
Embodiment 7: epiphysin preparation improves sleep function test
1 material and method
1.1 samples: the epiphysin preparation A improving sleep being prepared by embodiment 1, specification is 0.4g/ piece.Put shady and cool dry and comfortable
Ventilation preserves.People is oral recommends consumption to be everyone (adult) every day 1 time, and 1 every time, adult's body weight press 60kg calculating, converts into
Dosage is 6.7mg/kg BW.
1.2 animals used as test and packet: select the cleaning grade (II level) of Guangxi Medical University's medical experiment animal center breeding
Healthy adult Male Kunming strain mice 192, body weight is 18~22 grams, animal used as test production licence number: SCXK osmanthus 2003-
0003.Every 48 mouse are 1 group, totally 4 groups, carry out respectively direct sleep laboratory, extend test yellow Jackets lengths of one's sleep, penta
Barbital sodium sub-threshold dose hypnosis test, barbital sodium Sleep Latency Test.
1.3 experimental situation conditions: animal used as test room temperature: 22~25 DEG C, relative humidity: 55~70%.Animal used as test makes
With credit number: SYXK osmanthus 2006-0001.
1.4 dosage choice and the epiphysin preparation A process improving sleep: the epiphysin preparation A's according to this improvement sleep
Human body recommends consumption, if the 33.6th, the 67.0th, 134.0mg/kg BW (be respectively equivalent to human body and recommend the 5th, the 10th, 20 times of consumption) 3
The test group of dosage, sets a negative control group simultaneously, often organizes 12 animals.Epiphysin preparation A because improving sleep is insoluble in
Water, therefore with 3% food starch solution preparation.Weigh the epiphysin preparation A of the 0.168th, the 0.335th, 0.670g improvement sleep respectively, respectively
Add 3% food starch solution to l00mL, mix, be made into the 1.68th, the 3.35th, 6.70mg/mL strength solution, give corresponding agent respectively
Amount treated animal gavage, gavage volume is 0.2mL/l0g BW, and negative control group gives isopyknic distilled water, every day gavage one
Secondary, continuous 30 days.
1.5 key instruments and reagent:
Instrument: animal platform balance, electronic analytical balance, stopwatch etc..
Reagent: yellow Jackets (lot number: F20030816), barbital sodium (lot number: 20040428), Chinese Medicine (collection
Group) the import packing of Solution on Chemical Reagents in Shanghai company.
1.6 experimental techniques:
1.6.1 direct sleep laboratory: observe the sleep quality of mouse after to last sample, disappear with the righting reflex of animal
Quenching 60 seconds and being judged to enter sleep, righting reflex recovers to be animal awakening.Result X2Inspection carries out statistical analysis.Such as examination
Test group sleep number of animals and the length of one's sleep increases and has significant difference with negative control group, i.e. judge this result of the test as sun
Property.
1.6.2 the yellow Jackets test length of one's sleep is extended: after to last sample 20 minutes, each treated animal is noted through abdominal cavity
Penetrating yellow Jackets 45mg/kg BW, injection volume is 0.2mL/20g BW.With the righting reflex loss of animal as index, observation changes
Can the epiphysin preparation A of kind sleep extend yellow Jackets lengths of one's sleep.Result variance analysis carries out statistical analysis.Such as examination
The length of one's sleep testing group mouse extends and statistically significant than negative control group, i.e. judges this result of the test as the positive.
1.6.3 yellow Jackets sub-threshold dose hypnosis test: after to last sample 20 minutes, each treated animal is noted through abdominal cavity
Penetrate yellow Jackets 30mg/kg BW.The sleep quality of mouse in observing 30 minutes, with righting reflex loss, more than 60 seconds persons are
Fall asleep, record the sleep number of animals of each group, calculate sleep animal incidence.Result X2Check analysis.As test group is fallen asleep dynamic
Thing incidence is higher than negative control group statistically significant, i.e. judges this result of the test as the positive.
1.6.4 barbital sodium Sleep latency experiment: each treated animal after to last sample 20 minutes through lumbar injection bar
The appropriate sodium 300mg/kg BW of ratio, injection volume is 0.2mL/20g BW.With righting reflex loss as index, observe and improve taking off of sleep
Can melanocyte preparation A shorten barbital sodium Sleep latency.Result variance analysis carries out statistical analysis.Such as test group mouse
Sleep latency shortens and statistically significant than negative control group, i.e. judges this result of the test as the positive.
1.7 results judge
If mesh slept by the prolongation yellow Jackets experiment length of one's sleep, yellow Jackets sub-threshold dose hypnosis experiment, barbital sodium
It is positive that the people test binomial in three experiments incubation period, and without substantially direct sleep effect, can determine that the epiphysin that this improvement is slept
Preparation A has and improves sleep function effect.
2 results
2.1 improve the impact on Mouse Weight for the epiphysin preparation A of sleep
The epiphysin preparation A that table 1 improves sleep improves sleep function test mice body weight
Note: P value represents that each dosage group tests initial, mid-term and Mouse Weight and the weightening finish in latter stage are compared with control group, poor
It is different that there are no significant.
From table 1, experiment initial stage, experiment mid-term, experiment improve the little of each dosage group of epiphysin preparation A of sleep latter stage
Mouse Weight growth during mouse body weight and experiment is compared with between negative control group, and there are no significant for difference (P > 0.05), shows this
Improve the body weight growth to mouse for the epiphysin preparation A sleeping to have no significant effect.
The direct sleep effect of the 2.2 epiphysin preparation A improving sleep
As seen from Table 2, per os gives epiphysin preparation A30 days improving sleep of mouse various dose, and each dosage group is equal
Do not have animal righting reflex loss occur, i.e. all animals does not all enter into sleep state, points out the epiphysin that this improvement is slept
Preparation A does not has the effect that direct inducing mouse is slept.
Table 2 improves the direct sleep laboratory result of epiphysin preparation A mouse of sleep
2.3 improve the impact on the yellow Jackets length of one's sleep for the epiphysin preparation A of sleep
The epiphysin preparation A that table 3 improves sleep extends the yellow Jackets result of the test length of one's sleep
As seen from Table 3, per os gives epiphysin preparation A30 days improving sleep of mouse various dose, and each dosage group is little
The length of one's sleep of mouse all extends than negative control group, and dosage group high, middle therein has conspicuousness with the difference of negative control group
(respectively P < 0.01 and P < 0.05), the epiphysin preparation A pointing out this improvement sleep has prolongation yellow Jackets lengths of one's sleep
Effect.
2.4 improve the impact on yellow Jackets sub-threshold dose syngignoscism for the epiphysin preparation A of sleep
As seen from Table 4, per os gives epiphysin preparation A30 days improving sleep of mouse various dose, each dosage group
Animal sleep rate is higher than negative control group, and high dose group therein has conspicuousness (P < 0.05) with the difference of negative control group,
The epiphysin preparation A pointing out this improvement to sleep plays the role of collaborative hypnosis with the yellow Jackets of sub-threshold dose.
Table 4 improves the epiphysin preparation A yellow Jackets sub-threshold dose hypnosis test result of sleep
The 2.5 epiphysin preparation A preclinical impacts on barbital sodium hypnosis improving sleep
Table 5 improves the epiphysin preparation A barbital sodium Sleep Latency Test result of sleep
As seen from Table 5, per os gives the epiphysin preparation A 30 days improving sleep of mouse various dose, and each dosage group is little
The all ratio shortenings of negative control group of the Sleep latency of mouse, and the difference of each dosage group and negative control group is respectively provided with conspicuousness (P
< 0.01 or P < 0.05), the epiphysin preparation A pointing out this improvement to sleep has the effect that Sleep latency slept by shortening barbital sodium.
3 results judge
Respectively with the 33.6th, the 67.0th, the changing of 134.0mg/kg BW (be equivalent to human body and recommend the 5th, the 10th, 20 times of consumption) dosage
The epiphysin preparation A of kind sleep gives mouse stomach 30 days continuously, can extend yellow Jackets lengths of one's sleep, collaborative yellow Jackets
Sub-threshold dose syngignoscism, shorten barbital sodium Sleep latency, without direct sleep effect, on the body weight of mouse without impact, carry
Show that the epiphysin preparation A that this improvement is slept has the function improving sleep.
The epiphysin preparation B~E of embodiment 2~embodiment 5 also draws identical conclusion.
Claims (8)
1. the epiphysin preparation improving sleep, it is characterised in that include the raw material of following weight portion, epiphysin 1~3 part,
Starch 130~170 parts, white granulated sugar 100~156 parts, 70~144 parts of dextrin, talcum powder 2~6 parts, magnesium stearate 2~6 parts and carboxylic
Sodium carboxymethylcellulose pyce 0.2~2 part.
2. the epiphysin preparation improving sleep according to claim 1, it is characterised in that include the former of following weight portion
Material is epiphysin 2~3 parts, starch 150~170 parts, white granulated sugar 120~150 parts, 90~130 parts of dextrin, talcum powder 4~5 parts, hard
Fatty acid magnesium 4~6 parts and sodium carboxymethylcellulose 0.5~1 part.
3. the epiphysin preparation improving sleep according to claim 2, it is characterised in that include the former of following weight portion
Material, epiphysin 3 parts, starch 150 parts, white granulated sugar 128 parts, 110 parts of dextrin, talcum powder 4 parts, magnesium stearate 4 parts and carboxymethyl are fine
Dimension 1 part of sodium of element.
4. the epiphysin preparation improving sleep according to claim the 1st, 2 or 3, it is characterised in that by weight, also wrap
Include film coating agent 8~16 parts.
5. the epiphysin preparation improving sleep according to claim 4, it is characterised in that described film coating agent, bag
Include the raw material of following weight portion: Hydroxypropyl methylcellulose 3.6 parts, talcum powder 3.6 parts, titanium dioxide 0.8 part, 1,2-PD 1.3
Part and Tween-80 1.3 parts.
6. the preparation method of claim the 1st, the epiphysin preparation improving sleep described in 2 or 3, it is characterised in that include
Following steps: a) as described in claim the 1st, 2 or 3 improve sleep epiphysin preparation in required weight portion weigh respectively take off black
Element, starch, dextrin, white granulated sugar, talcum powder and magnesium stearate sieve after pulverizing;B) sodium carboxymethylcellulose by required weight portion
Be dissolved in the water to obtain sodium carboxymethylcellulose slurry;C) mixture is obtained after epiphysin, starch, dextrin and white granulated sugar being mixed
Material;D) mixing mixed material with sodium carboxymethylcellulose slurry, through pelletizing, grain dry, whole obtains dry particle;E) by dry
Grain obtains, after mixing with talcum powder, magnesium stearate, the material always mixing, and obtains improving the epiphysin system of sleep through compressing tablet, coating
Agent.
7. preparation method according to claim 6, it is characterised in that described sodium carboxymethylcellulose slurry is mass fraction
It is the sodium carboxymethylcellulose slurry of 2%.
8. preparation method according to claim 6, it is characterised in that described by epiphysin, starch, dextrin and white granulated sugar
After mixing mixed material is first to mix epiphysin and starch by equal increments mixing method, then with dextrin, white
Granulated sugar obtains mixed material after mixing.
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CN111407761A (en) * | 2020-04-28 | 2020-07-14 | 广东润源中天生物科技有限公司 | Melatonin vitamin B6 tablet and production method thereof |
CN114246834A (en) * | 2021-12-30 | 2022-03-29 | 宣城柏维力生物工程有限公司 | Melatonin orally disintegrating preparation for improving sleep and production process thereof |
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CN105663061A (en) * | 2014-11-16 | 2016-06-15 | 刘佳迪 | Preparation method and application method for melatonin dropping pill |
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CN101143135A (en) * | 2007-10-10 | 2008-03-19 | 徐贵丽 | Melatonin orally disintegrating tablet and preparation method thereof |
CN104248630A (en) * | 2014-09-11 | 2014-12-31 | 常州欧法玛制药技术有限公司 | Melatonin-containing double-layered osmotic pump controlled release tablet and preparation method thereof |
CN105663061A (en) * | 2014-11-16 | 2016-06-15 | 刘佳迪 | Preparation method and application method for melatonin dropping pill |
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CN111407761A (en) * | 2020-04-28 | 2020-07-14 | 广东润源中天生物科技有限公司 | Melatonin vitamin B6 tablet and production method thereof |
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CN114246834A (en) * | 2021-12-30 | 2022-03-29 | 宣城柏维力生物工程有限公司 | Melatonin orally disintegrating preparation for improving sleep and production process thereof |
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