CN1491693A - Extraction of wild jujube seed oil and preparation of soft capsule and function on central nervous system - Google Patents
Extraction of wild jujube seed oil and preparation of soft capsule and function on central nervous system Download PDFInfo
- Publication number
- CN1491693A CN1491693A CNA031345581A CN03134558A CN1491693A CN 1491693 A CN1491693 A CN 1491693A CN A031345581 A CNA031345581 A CN A031345581A CN 03134558 A CN03134558 A CN 03134558A CN 1491693 A CN1491693 A CN 1491693A
- Authority
- CN
- China
- Prior art keywords
- ziziphi spinosae
- semen ziziphi
- oil
- spinosae oil
- wild jujube
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention provides the extraction of wild jujube seed oil, the preparation of soft capsule and the function on central nervous system. The extraction of wild jujube seed oil includes squeezing wild jujube seed in squeezer to obtain dregs and coarse oil; mixing the dregs and petroleum ether to obtain refined oil after recovering petroleum ether; dissolving the coarse oil and petroleum ether to obtain refined oil after recovering petroleum ether; merging refined oil, heating in evaporating pot to eliminate residual solvent and water and to obtain wild jujube seed oil. The preparation of soft wild jujube seed oil capsule includes soaking gelatin, heating in water bath, adding glycerin and Nipagin A, and filtering to obtain gelatin liquid; preparing gelatin plate with the gelatin liquid; sandwiching wild jujube seed oil with two gelatin plates and pressing with steel mold. Research shows that wild jujube seed oil has tranquilizing, hypnotic, memory-promoting and anxiety resisting effects, and may be used in treating neurosis and insomnia.
Description
One, technical field
The present invention relates to preparation technology of a kind of medicine and uses thereof, particularly the extraction of Semen Ziziphi Spinosae oil and preparation of soft capsule reach the effect to the central nervous system.
Two, background technology
Semen Ziziphi Spinosae is the Chinese crude drug that is usually used in tranquilizing by nourishing the heart, is used for Chinese medicine compound more.It is generally acknowledged the water soluble part of Semen Ziziphi Spinosae---the Semen Ziziphi Spinosae total glycosides is that Semen Ziziphi Spinosae is to the neurergic effective site of maincenter.Semen Ziziphi Spinosae oil often is dropped as invalid target.Existing patent application: 1) prescription of wild jujube kernel oil pellet for lowering blood fat and preparation method thereof (94107184), content comprises the preparation of Semen Ziziphi Spinosae oil drop pill and the purposes of blood lipid regulation; 2) supercritical carbon dioxide extraction method extracts Semen Ziziphi Spinosae oil and spiny jujuba seed powder (00104496), and content comprises the extracting method of Semen Ziziphi Spinosae oil.Above-mentioned patent exists shortcomings such as technology cost height, and supercritical carbon dioxide extraction method needs special equipment.
Three, summary of the invention
The object of the present invention is to provide the extraction and the preparation of soft capsule method of a kind of extraction and the simple Semen Ziziphi Spinosae oil of preparation technology.
Another object of the present invention is to verify of the effect of Semen Ziziphi Spinosae oil soft capsule to the central nervous system.
The extraction process that adopts for the present invention that achieves the above object is: the Semen Ziziphi Spinosae that at first will remove moisture and nucleocapsid is broken into coarse powder, puts on the squeezer and squeezes, and till pressing no oil stream and going out, obtains the residue and the crude product oil of Semen Ziziphi Spinosae; With the mixed that the residue and the petroleum ether of Semen Ziziphi Spinosae is 1: 2.5 by volume, extracted 1.5 hours, reclaim petroleum ether, obtain refining oils and fats; The crude product oil that squeezing is obtained adds in the petroleum ether of 4 times of volumes and carries out dissolution filter, reclaims petroleum ether to tasteless, discards residue and obtains refining oils and fats; The refining oils and fats of two parts being merged, obtains the clarifying thickness oily liquids of a kind of yellow---Semen Ziziphi Spinosae oil, Semen Ziziphi Spinosae oil place evaporation boiler to heat 2 hours down at 110 ℃, fling to residual solvent and moisture, promptly get and make with extra care light yellow clear and bright Semen Ziziphi Spinosae oil.
Semen Ziziphi Spinosae oil preparation of soft capsule technology is: at first 200 parts of gelatin are soaked in the mid-water-bath of back dislocation flask with 55～65 ℃ of heating with 350 parts pure water, evenly stirred 10 minutes, obtain colloidal sol; In colloidal sol, add 80 parts of glycerol and 0.03 part to the carboxyl ethyl benzoate, at room temperature leave standstill 30min after, in the reduced vacuum of 600～650mmHg, scrape off the come-up foam, filter that to make glue stand-by; Glue is made offset plate, again 500 parts of Semen Ziziphi Spinosae oil are placed between two blocks of offset plates, suppress with punching block, peck every Semen Ziziphi Spinosae oil capsule of accurate control by the filling pump chilblain and contain Semen Ziziphi Spinosae oil 0.5g, the Semen Ziziphi Spinosae oil capsule that makes is placed dry 24h under 27～29 ℃, the condition of relative humidity 40%, promptly get every seed lac ball and include Semen Ziziphi Spinosae oil 500mg.
The present invention is by having verified that to pharmacology, the toxicologic study of Semen Ziziphi Spinosae oil Semen Ziziphi Spinosae oil has calmness, hypnosis, promotion learning and memory and angst resistance effect, can be used for treating neurasthenia and insomnia.
Four, the specific embodiment
1. determine that Semen Ziziphi Spinosae oil is the effective site of Semen Ziziphi Spinosae central nervous system effect
Semen Ziziphi Spinosae oil has been carried out the saponification esterification, and the extraction separation of fatty oil and betulinic acid obtains non-saponification resultant, esterification product, fatty oil and the betulinic acid crystallization of Semen Ziziphi Spinosae oil; The above-mentioned product of Semen Ziziphi Spinosae oil is carried out the pharmacologically active screening of sedation, the result shows, except that the non-saponification resultant non-activity of Semen Ziziphi Spinosae oil, fatty oil, betulinic acid all have sedation when the dosage on year-on-year basis of Semen Ziziphi Spinosae oil, the effective site that shows the Semen Ziziphi Spinosae tranquilizing soporific may be fatty acid and and be dissolved in betulinic acid in the fatty acid, experimental result sees Table 1.
Table 1 Semen Ziziphi Spinosae oil unsaponifiable matter, esterification product and betulinic acid are to the influence of spontaneous activity in mice
After the preceding administration of administration
Dosage
The movable number rate of change of group activity number
(/kg)
(inferior/10min) (inferior/10min)
Water--827.75 ± 95.19 834.75 ± 92.20 0.02 ± 0.20
Excipient--856.75 ± 76.28 835.25 ± 88.41-0.02 ± 0.13
1.65mg 882.25 ± 162.30 355.00 ± 129.12 are dissolved on ground
*-0.60 ± 0.13
*
III
A(fatty oil) 0.7ml 797.25 ± 216.74 575.50 ± 116.91
*-0.34 ± 0.14
*
III
B(betulinic acid) 0.77mg (with making a gesture of measuring) 896.75 ± 76.95 625.00 ± 131.46
*-0.31 ± 0.10
*
I organizes (non-saponification) 0.175ml 716.0 ± 204.6 800.5 ± 147.1 0.15 ± 0.22
II organizes (esterification) 0.175ml 692.0 ± 193.9 748.5 ± 74.5
*0.02 ± 0.29
*
0.35ml 793.0±102.6 515.6±154.7
** -0.26±0.13
**
X ± s (n=12); II group, III
AGroup, III
BGroup compares with vehicle group.I group, diazepam group and water matched group compare,
*P＜0.05;
*P＜0.01.
Table 1 shows that the fatty oil of Semen Ziziphi Spinosae, esterification product and betulinic acid can reduce the spontaneous activity of mice, have sedation; And unsaponifiable matter does not have sedation, illustrate that Semen Ziziphi Spinosae oil and liposoluble substance thereof (betulinic acid) are the effective site of Semen Ziziphi Spinosae central nervous system effect, and the non-saponification part (water-soluble portion) of Semen Ziziphi Spinosae does not have sedation.
2. the extraction process of Semen Ziziphi Spinosae oil
The Semen Ziziphi Spinosae oil leaching process is followed successively by: squeeze, extract and make with extra care, extraction process of the present invention is with low cost, and the extraction ratio height does not have obvious environmental pollution.
1) squeezes the Semen Ziziphi Spinosae that to remove moisture and nucleocapsid and be broken into coarse powder, put on the squeezer and squeeze, till pressing no oil stream and going out, obtain the residue and the crude product oil of Semen Ziziphi Spinosae;
2) extract the design of application orthogonal experiment leaching process has been carried out optimizing research, with solvent, dosage, extraction time is that technology is investigated object, with the Semen Ziziphi Spinosae oil extraction ratio is index, adopts range method and method of analysis of variance to carry out date processing, the extraction process of preferred Semen Ziziphi Spinosae oil.Studies show that with petroleum ether the Semen Ziziphi Spinosae residue being extracted 1.5 hours with 1: 2.5 volume ratio is optimum extraction condition, reclaim petroleum ether, obtain refining oils and fats; Temperature does not have obviously influence to extracting in the extraction;
3) the refining crude product oil that squeezing is obtained adds in the petroleum ether of 4 times of volumes and carries out dissolution filter, reclaims petroleum ether to tasteless, discards residue and obtains refining oils and fats.The refining oils and fats of two parts is merged, obtain the clarifying thickness oily liquids of a kind of yellow---Semen Ziziphi Spinosae oil, place evaporation boiler with 110 ℃ of heating 2 hours Semen Ziziphi Spinosae oil, fling to residual solvent and moisture, promptly get and make with extra care light yellow clear and bright refined oil.
2. Semen Ziziphi Spinosae oil preparation of soft capsule technology; Adopt pressing
1) formula proportion: 500 parts of Semen Ziziphi Spinosae oil, 200 parts in gelatin, 80 parts of glycerol, to 0.03 part of carboxyl ethyl benzoate, 350 parts of pure water;
2) colloidal sol preparation: earlier 200 parts of gelatin are added in the mid-water-bath of flask of soaking back dislocation band jacketed pan in 350 parts of pure water before the preparation and heat, heating-up temperature is 55～65 ℃, evenly stirred 10 minutes, add 80 parts of glycerol and 0.03 part of ethylparaben after the DANGMING peptizationization, stirring makes to dissolve becomes even glue, leaves standstill 30min at normal temperatures, scrapes off the come-up foam in the reduced vacuum of 600～650mmHg, recording gelatin viscosity is 27000mpaS, and it is stand-by that glue is made in filtration;
3) preparation of Semen Ziziphi Spinosae oil soft capsule: adopt the milling process preparation
Soft capsule preparation: glue is made offset plate, again Semen Ziziphi Spinosae oil is placed between two blocks of offset plates, form with the punching block compacting.Continuous production, adopt rotation Zhanang machine (RJNJ-2) automatically, automatically two adhesive tapes being made by machine are with form continuously, move round about, before reaching rotating mould, move closer to, a part is through pressurization and combination, this moment, Semen Ziziphi Spinosae oil then was pressed into by the wedge shape ascending pipe between two bands through conduit from filling pump, 21～25 ℃ of room temperatures, under relative humidity 40% condition, moving by the not stall of rotating mould, then adhesive tape and medicinal liquid are pressed in the groove of mould, the groove temperature is about 60 ℃, makes the whole roll compacting combinations of adhesive tape, medicinal liquid is wrapped in wherein forms the Semen Ziziphi Spinosae oil capsule.Peck accurate control Semen Ziziphi Spinosae oil mass 0.5g by the filling pump chilblain, remaining adhesive tape is automatic cutting and separating.
Whole ball is with dry: granulate is checked outward appearance, should be clean and tidy, and do not have the bonding distortion, break and the embrittlement phenomenon, put 27～29 ℃ of temperature, with the dry 24h of oily ball, promptly get oil-containing 500mg in every seed lac ball under relative humidity 40% condition.
Store: should be airtight and put shady and cool dry place and store, storage temperature generally should not surpass 25 ℃, and relative humidity is no more than 45%.
Result: character: this product is faint yellow transparent soft capsule, remove the soft gelatin capsule shell after, content is the pale yellow oily liquid body; Content uniformity: qualified; Disintegration: qualified; Content: 99.5%; Conclusion: by the sample of process trial of the present invention, every detection index all meets the requirements, outward appearance U.S. particularly, and the softgel shell compacting is evenly, and is oil-tight.
Usage and consumption: be used for malaise and insomnia forgetfulness patient, oral one day 2 times, each 3 balls; Add 4 balls before sleeping in case of necessity.
The main pharmacodynamics research of Semen Ziziphi Spinosae oil: research project is as follows:
1) sedation (to the influence of mice autonomic activities): 1. photoelectric method (single and repetitively administered); 2. unsteady method; 3. knockout method.
Pharmacodynamic result shows: carried out the influence of mice autonomic activities is tested with photoelectric method, the method for floating, knockout method, the result shows: (0.35～1.4ml/kg i.g.), makes mice present movable the minimizing to Semen Ziziphi Spinosae oil, have certain sedation, and use 10 days no tolerations continuously.See Table 2, table 3, table 4.
Table 2 Semen Ziziphi Spinosae oil to the mice autonomic activities (movable number: inferior/10min) influence X ± S (n=14)
After the preceding administration of group dosed administration
(/kg) d
1 d
5 d
10
Water 20ml 991.0 ± 25.5 955.5 ± 27.2 933.3 ± 23.6 952.3 ± 41.8
(-3.6±1.8) (-5.7±4.8) (-3.9±4.6)
Emulsion 20ml 967.3 ± 44.7 971.4 ± 73.4 928.7 ± 101.3 980.0 ± 63.8
(2.4±0.4) (-2.8±1.3) (1.0±1.1)
Diazepam 1.65mg 976.0 ± 53.6 284.3 ± 55.4
*210.0 ± 73.3
*237.4 ± 23.0
*
(-70.6±7.0
**) (-78.7±6.9
**) (-75.7±2.1
**)
Rhizoma Gastrodiae 40mg 970.5 ± 36.3 867.5 ± 233.0 659.3 ± 90.6
*765.8 ± 158.3
*
(-10.3±25.5
**) (-31.9±10.2
**) (-20.8±18.0
**)
Semen Ziziphi Spinosae oil 0.35ml 963.0 ± 34.6 794.8 ± 150.1
*610.3 ± 144.8
*575.3 ± 53.9
*
(-17.3±16.7
**) (-36.2±17.2
**) (-42.7±9.2
**)
0.7ml 956.5±30.7 734.5±131.7
** 627.8±58.8
** 733.3±165.2
**
(-23.4±11.5
**) (-34.4±5.4
**) (-23.6±15.9
**)
1.4ml 974.3±75.3 802.8±197.2
* 624.3±110.1
** 468.5±53.9
**
(-17.63±19.2
**) (-36.1±9.1
**) (-51.9±4.6
**)
Semen Ziziphi Spinosae total glycosides 0.2g 934.3 ± 43.7 972.2 ± 217.5 925.1 ± 131.9 915.6 ± 75.7
(37.2±42.1) (-6.9±12.3) (21.5±17.6)
In the bracket () is rate of change, and diazepam group and Rhizoma Gastrodiae group and water matched group are relatively; Semen Ziziphi Spinosae line of oils and emulsion group be * P＜0.05 relatively, * * P＜0.01
Experimental result shows shown in the table 2: the autonomic activities of Semen Ziziphi Spinosae line of oils (0.35,0.7,1.4ml/kg) mice reduces (P＜0.01), and does not see with the effect of the prolongation Semen Ziziphi Spinosae oil of administration time and to weaken, and does not show Drug tolerance.The prompting Semen Ziziphi Spinosae oil has sedation to mice, and its sedation does not have toleration.Do not present dependence between drug dose and the drug effect.Semen Ziziphi Spinosae oil some mice of heavy dose of group (4/12) begins to occur reposing motionless and short time (in 10 seconds) righting reflex loss phenomenon along with administration time prolongs, and can revive after the stimulation.Semen Ziziphi Spinosae total saponins (0.2g/kg) does not show sedation, the suitable crude drug amount of this dosage 25g/kg.As seen Semen Ziziphi Spinosae oil is the main effective site of Semen Ziziphi Spinosae tranquilizing by nourishing the heart and tranquilizing soporific, and Semen Ziziphi Spinosae total saponins is not.
Table 3 Semen Ziziphi Spinosae oil is to white mice autonomic activities area under curve (cm
2) influence (float method)
After the administration
Before the dosed administration
n 1d 2d 3d
Excipient 16-23 ± 3 21.1 ± 0.8 23 ± 10 16 ± 4
Sodium phenobarbital 12 10mg/kg 27 ± 4 10 ± 10
*2.8 ± 2.6
*0
Semen Ziziphi Spinosae oil 12 1.4ml/kg 26.4 ± 2.5 8.1 ± 2.9
*2.9 ± 1.8
*6.9 ± 2.7
*
Semen Ziziphi Spinosae oil 12 0.35ml/kg 25 ± 8 17 ± 3
*6.0 ± 1.1
*8.0 ± 3.1
*
X ± s compares with excipient,
*P＜0.01
Table 4 Semen Ziziphi Spinosae oil is to the fall influence of husky amount (ml) of white mice autonomic activities
Dosage
After the administration (d)
Before the N administration
(/kg) 1 2 3
Excipient 16 20ml 8.4 ± 0.6 7.4 ± 1.1 6.4 ± 1.1 5.5 ± 0.7
Semen Ziziphi Spinosae oil 12 1.4ml 8.5 ± 0.3 7.1 ± 0.3 5.0 ± 1.0
*5.3 ± 1.3
Semen Ziziphi Spinosae oil 12 0.35ml 8.4 ± 0.1 5.6 ± 0.3
*5.3 ± 0.3
*4.7 ± 1.2
*
X ± s compares with matched group,
*P＜0.05,
*P＜0.01.
Experimental result shows shown in table 3, the table 4: and Semen Ziziphi Spinosae oil (0.35,1.4ml/kg) the white mice autonomic activities is obviously reduced, relatively there were significant differences (P＜0.01) with matched group, illustrates that Semen Ziziphi Spinosae oil has tangible sedation.
2) syngignoscism: the research experiment method comprises: the 1. collaborative pentobarbital sodium hypnosis time; 2. reenter the experiment of sleeping; 3. inducing mouse sleep.
The syngignoscism result of study shows: 1. (0.35～1.4ml/kg) can prolong the sleep of pentobarbital sodium induced mice to Semen Ziziphi Spinosae oil, and has dose-dependence and see Table 5; 2. reenter the number of animals of sleeping after with the dosage Semen Ziziphi Spinosae oil pentobarbital sodium mice being waken up and increase and see Table 6, prompting Semen Ziziphi Spinosae oil and pentobarbital sodium have collaborative syngignoscism; 3. Semen Ziziphi Spinosae oil (1.4～5.6ml/kg) can make the mice righting reflex loss, stimulate the back mice to revive, illustrate Semen Ziziphi Spinosae oil directly inducing mouse enter sleep; Successive administration 10 days, along with administration time prolongs, the mice induced hypnotic shortens incubation period gradually, prolong the length of one's sleep gradually, and has certain dose-effect relationship and see Table 7, and the prompting Semen Ziziphi Spinosae oil has sedative-hypnotic effect, and for a long time with no toleration.
Table 5 Semen Ziziphi Spinosae oil is to the influence of the pentobarbital sodium length of one's sleep (min)
The group example number dosage P length of one's sleep
Water matched group 14 20ml/kg 7.07 ± 4.56:
Emulsion matched group 14 20ml/kg 6.83 ± 4.87:
Diazepam group 14 3.3mg/kg 128.64 ± 12.60＜0.01
Whole day fiber crops group 14 40mg/kg 60.78 ± 11.25＜0.01
Semen Ziziphi Spinosae oil
Low dose of 14 0.35ml/kg 21.71 ± 5.74＜0.01
Middle dosage 14 0.7ml/kg 36.92 ± 7.96＜0.01
Heavy dose of 14 1.4ml/kg 52.93 ± 7.34＜0.01
X ± s: contrast groups, diazepam group and whole day fiber crops group compare with the water matched group; Semen Ziziphi Spinosae line of oils and vehicle group are relatively carried out statistical analysis and are done the dose-effect relationship analysis with t check between group.
Table 6 Semen Ziziphi Spinosae oil to mice sleeping again (only/50min) influence x ± s
Group n dosage reenters the number of animals P that sleeps
Water matched group 14 20ml/kg 1:
Emulsion matched group 14 20ml/kg 0:
Diazepam group 14 3.3mg/kg 14 0.002
Whole day fiber crops group 14 40mg/kg 6 0.08
Semen Ziziphi Spinosae oil
Low dose of 14 0.35ml/kg 3 0.27
Middle dosage 14 0.7ml/kg 6 0.0399
Heavy dose of 14 1.4ml/kg 7 0.0211
Table 7 Semen Ziziphi Spinosae oil is to the influence of mice sleep inducing incubation period and time (min)
Behind the group n dosed administration
(/kg) d
1 d
5 d
10
Sleep inducing incubation period
Water matched group 14-∞ ∞ ∞
Vehicle group 14-∞ ∞ ∞
Diazepam group 14 3.3mg 17.5 ± 5.8
++29.1 ± 6.1
++38.6 ± 3.7
++
Rhizoma Gastrodiae group 14 80mg 30.5 ± 6.6
++ * *24.3 ± 4.2
++ *25.4 ± 8.9
++ * *
Semen Ziziphi Spinosae oil
Small dose group 14 1.4ml ∞ 45.6 ± 6.7
++ * *40.3 ± 10.7
++ * *
Middle dosage group 14 2.8ml ∞ 31.4 ± 4.9
++31.1 ± 5.9
++ * *
Heavy dose of group 14 5.6ml 41.6 ± 6.4
++ * *25.6 ± 5.1
++20.4 ± 5.9
++ * *
The induced hypnotic time
Water matched group 14-0
00
Vehicle group 14-0 00
Diazepam group 14 3.3mg 46.6 ± 11.2
++32.4 ± 5.0
++18.1 ± 4.0
++
Rhizoma Gastrodiae group 14 80mg 8.1 ± 2.9
++13.9 ± 4.5
++ * *23.6 ± 4.5
++ * *
Semen Ziziphi Spinosae oil
Small dose group 14 1.4ml 0 7.1 ± 3.1
++ * *11.2 ± 4.5
++ * *
Middle dosage group 14 2.8ml 0 20.1 ± 3.7
++ * *29.4 ± 6.1
++ * *
Heavy dose of group 14 5.6ml 5.7 ± 2.9
++ * *21.1 ± 3.7
++ * *40.3 ± 4.5
++ * *
X ± s, diazepam and Rhizoma Gastrodiae group and water are compared, and Semen Ziziphi Spinosae oil and vehicle group compare,
++P＜0.01; Compare with the diazepam group,
*P＜0.05,
*P＜0.01; Owing to contain underrange, should carry out date processing with preface value method.
Shown in the table 7, Semen Ziziphi Spinosae oil shortens dropping asleep latency, and prolonged the length of one's sleep, and its effect has certain dose-dependence, and the medication effect is tending towards obviously repeatedly, illustrates that the syngignoscism of Semen Ziziphi Spinosae oil does not have toleration.After the medication, effect is tending towards weakening diazepam, shows tolerific untoward reaction repeatedly.
3) promote the learning and memory effect: 1. keep away silent method and see Table 8; 2. the diving tower method sees Table 9;
Employing keeps away silent method and the diving tower method studies show that: (0.175～0.7ml/kg) can make prolongation of latency normal and that the dysmnesia mice is made the learning and memory mistake to Semen Ziziphi Spinosae oil, and errors number reduces, and the prompting Semen Ziziphi Spinosae oil can be strengthened the learning and memory function of mice.It is stronger that twice experiment all presents middle dosage effect, and the inverted U dose-effect relationship that large and small dosage effect is more weak illustrates and uses the promotion learning and memory effect of Semen Ziziphi Spinosae oil that certain dosage range is arranged.
Table 8 Semen Ziziphi Spinosae oil is to influence (darkness avoidance test) x ± s (n=14) of learning and memory of little mouse
After training before the dosage training
Group (/kg) incubation period number of shocks number of shocks incubation period
(sec) (inferior/5min) (sec) (inferior/5min)
The water matched group--24.3 ± 9.0 3.41 ± 1.03 99.7 ± 33.6
The Δ Δ+1.83 ± 1.07
The Δ Δ
Vehicle group--23.7 ± 5.7 3.74 ± 0.95 92.4 ± 38.7
The Δ Δ1.79 ± 0.98
The Δ Δ
Stable group--27.6 ± 7.8 3.82 ± 1.24 30.7 ± 17.2
*3.16 ± 0.98
*
Rhizoma Gastrodiae group 40mg 21.9 ± 8.5 3.28 ± 1.03 190.7 ± 81.4
*0.83 ± 0.37
*
Semen Ziziphi Spinosae oil
Low dose of 0.175ml 24.5 ± 5.0 3.43 ± 0.90 165.5 ± 78.3
*1.33 ± 0.94
Middle dosage 0.35ml 21.6 ± 10.4 3.39 ± 0.70 179.2 ± 110.7
*0.83 ± 0.69
*
Heavy dose of 0.7ml 22.7 ± 4.2 3.47 ± 0.93 216.7 ± 84.7
*1.33 ± 1.24
It is relatively preceding with training,
The Δ ΔP＜0.01; Diazepam and Rhizoma Gastrodiae group and water are compared, and Semen Ziziphi Spinosae oil and vehicle group compare,
*P＜0.05,
*P＜0.01
Table 9 Semen Ziziphi Spinosae oil is to influence (diving tower method) x ± s (n=14) of learning and memory of little mouse
After training before the training
Group dosage (/kg) errors number rate of change incubation period errors number rate of change
(inferior/5min) (sec) (%) (inferior/5min) (%)
The water contrast--3.00 ± 0.63 212.6 ± 24.9
*155 1.40 ± 0.55
* Δ Δ-53
Excipient--3.16 ± 0.93 208.5 ± 37.6
*265 1.27 ± 0.64
* Δ Δ-58
Model--3.12 ± 1.29 57.2 ± 28.1 3.00 ± 0.89
Whole day fiber crops 40ml 3.25 ± 1.39 258.4 ± 22.1
*351 0.88 ± 0.35
*-70
Semen Ziziphi Spinosae oil
Low dose of 0.175ml 2.75 ± 1.28 237.4 ± 55.8
*314 0.80 ± 0.45
*-73
Middle dosage 0.35ml 3.38 ± 1.75 263.6 ± 42.1
*361 0.50 ± 0.53
*-83
Heavy dose of 0.7ml 2.80 ± 0.84 257.8 ± 40.3
*349 0.63 ± 0.52
*-79
Relatively preceding with training, paired t-test
The Δ ΔP＜0.01; Compare non-paired t test with model group
*P＜0.01
4) angst resistance effect:
1. convulsion experiment: studies show that (the tangible anticonvulsant action of Semen Ziziphi Spinosae oil is not found in 0.35～1.4ml/kg) influence to strychnine and pentetrazole convulsions to observe Semen Ziziphi Spinosae oil.
2. mice is divided into 5 groups at random, 8 every group: the normal saline contrast; Positive controls (stabilizing); Semen Ziziphi Spinosae oil heavy dose (2ml/kg), middle dosage (1ml/kg), low dose of (0.5ml/kg) group.Mice placed on the plate in 30 minutes after the administration, allow it probe into 15s.After this, mice is whenever giving once to shock by electricity when a plate is cross over another piece plate, and current intensity 0.35mA continues 0.5s.Therefore mice produces tangible escape reaction, passes 2 blocks of plates or 3 blocks of plates usually.Continue to run as mice, the 3min does not after this give electric shock.Shock count in the record 10min.Electric shock can make the active significantly minimizing of mouse movement, increases shock count, explanation but stabilize with the Semen Ziziphi Spinosae oil significance.Semen Ziziphi Spinosae oil has certain angst resistance effect and sees Table 10.
The angst resistance effect research (experiment of mice four plate methods) of table 10. Semen Ziziphi Spinosae oil (X ± S)
Group example number dosage electricity swashs number of times (10min)
NS matched group 10 5ml/kg 5.50 ± 1.92
Stable 10 1mg/kg 13.3 ± 1.74
*
Heavy dose of 8 2ml/kg 9.88 ± 2.42 of Semen Ziziphi Spinosae oil
*
Middle dosage 8 1ml/kg 10.0 ± 2.73
*
Low dose of 8 0.5ml/kg 9.13 ± 2.80
*
5) other effects: studies show that Semen Ziziphi Spinosae oil also has: strengthen the immune function of mice effect, to the antitumor action of tumor-bearing mice.
5. the safety research of Semen Ziziphi Spinosae oil
Acute toxicity test in mice: test shows, can't accurately record its LD with the mouse stomach administration
50The maximum dosage of the mice of Semen Ziziphi Spinosae oil gastric infusion is 286g (crude drug)/kg.d
-1, according to the weight, quite 591 times of the maximum dosage 29g/d on probation of adult (body weight 60kg).
Long term toxicity test: the dog long term toxicity test studies show that: continuous 90 days big dose application Semen Ziziphi Spinosae oil (2.0,6.0,20ml/kg) except that cause that obvious maincenter suppresses and oiliness diarrhoea, the overt toxicity of not observing dog reacts.The rat long term toxicity test studies show that: continuous 91 days big dose application Semen Ziziphi Spinosae oil (3.2,8.0,20ml/kg) are not observed the overt toxicity reaction of rat.
General pharmacology is learned research: studies show that, except the nervus centralis effect, (0.4～1.0ml/kg) has certain reduction effect to dog systolic blood pressure and respiratory frequency to heavy dose of Semen Ziziphi Spinosae oil, but it is less to reduce low amplitude, does not have tangible pharmacology and experimental therapeutic meaning.Semen Ziziphi Spinosae oil does not have the explicitly influence to dog heart rate, diastolic pressure and respiratory depth.General pharmacology research explanation, Semen Ziziphi Spinosae oil suppresses for the main pharmacodynamics effect except maincenter, does not find that other is to cardiovascular system the unify apparent side effect or the experimental therapy effect of respiratory system.
Claims (3)
1, the extraction process of Semen Ziziphi Spinosae oil is characterized in that:
1) squeezes the Semen Ziziphi Spinosae that at first will remove moisture and nucleocapsid and be broken into coarse powder, put on the squeezer and squeeze, till pressing no oil stream and going out, obtain the residue and the crude product oil of Semen Ziziphi Spinosae;
2) extract the mixed that residue and petroleum ether with Semen Ziziphi Spinosae are 1: 2.5 by volume, extracted 1.5 hours, the recovery petroleum ether obtains making with extra care oils and fats;
3) the refining crude product oil that squeezing is obtained adds in the petroleum ether of 4 times of volumes and carries out dissolution filter, reclaims petroleum ether to tasteless, discards residue and obtains refining oils and fats;
4) mix the refining oils and fats merging of two parts, obtain the clarifying thickness oily liquids of a kind of yellow---Semen Ziziphi Spinosae oil, Semen Ziziphi Spinosae oil places evaporation boiler to heat 2 hours down at 110 ℃, flings to residual solvent and moisture, promptly gets and makes with extra care light yellow clear and bright Semen Ziziphi Spinosae oil.
2, Semen Ziziphi Spinosae oil preparation of soft capsule technology is characterized in that:
1) at first 200 parts of gelatin is soaked in the mid-water-bath of back dislocation flask with 55～65 ℃ of heating with 350 parts pure water, evenly stirred 10 minutes, obtain colloidal sol;
2) in colloidal sol, add 80 parts of glycerol and 0.03 part to the carboxyl ethyl benzoate, at room temperature leave standstill 30min after, in the reduced vacuum of 600～650mmHg, scrape off the come-up foam, filter that to make glue stand-by;
3) glue is made offset plate, again 500 parts of Semen Ziziphi Spinosae oil are placed between two blocks of offset plates, suppress with punching block, peck every Semen Ziziphi Spinosae oil capsule of accurate control by the filling pump chilblain and contain Semen Ziziphi Spinosae oil 0.5g, the Semen Ziziphi Spinosae oil capsule that makes is placed dry 24h under 27～29 ℃, the condition of relative humidity 40%, promptly get every seed lac ball and include Semen Ziziphi Spinosae oil 500mg.
3, active ingredient has calmness, hypnosis, promotion learning and memory and angst resistance effect with the Semen Ziziphi Spinosae oil soft capsule of Semen Ziziphi Spinosae oil preparation, can be used for treating neurasthenia and insomnia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031345581A CN1491693A (en) | 2003-09-10 | 2003-09-10 | Extraction of wild jujube seed oil and preparation of soft capsule and function on central nervous system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031345581A CN1491693A (en) | 2003-09-10 | 2003-09-10 | Extraction of wild jujube seed oil and preparation of soft capsule and function on central nervous system |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1491693A true CN1491693A (en) | 2004-04-28 |
Family
ID=34239983
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031345581A Pending CN1491693A (en) | 2003-09-10 | 2003-09-10 | Extraction of wild jujube seed oil and preparation of soft capsule and function on central nervous system |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1491693A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229247B (en) * | 2007-12-28 | 2011-06-01 | 重庆理工大学 | Medicine preparation for treating insomnia and preparing method thereof |
| CN102258192A (en) * | 2011-07-11 | 2011-11-30 | 王跃进 | Enhanced red date soft capsule nutrition |
| CN103039962A (en) * | 2011-10-15 | 2013-04-17 | 北京以岭药业有限公司 | Jujube seed oil soft capsule and preparation method thereof |
| CN104886568A (en) * | 2015-05-13 | 2015-09-09 | 中国中轻国际工程有限公司 | Wild jujube seed oil soft capsule production technology |
| CN105106347A (en) * | 2015-06-26 | 2015-12-02 | 重庆医科大学 | Semen ziziphi spinosae soft capsules and preparation method thereof |
| CN105286013A (en) * | 2015-09-23 | 2016-02-03 | 安徽唐人药业有限公司 | Jujube kernel essential oil soft capsule and making method |
| CN105477100A (en) * | 2015-12-23 | 2016-04-13 | 无锡瑞盈生命科学有限公司 | Lucid ganoderma spore oil compound health care spray and preparation method |
| CN103039962B (en) * | 2011-10-15 | 2016-12-14 | 北京以岭药业有限公司 | A kind of Semen Ziziphi Spinosae oil soft capsule and preparation method thereof |
| WO2018045547A1 (en) * | 2016-09-09 | 2018-03-15 | 石家庄以岭药业股份有限公司 | Applications of jujube seed oil in treating medicinal insomnia |
| CN110419596A (en) * | 2019-08-21 | 2019-11-08 | 天津国际生物医药联合研究院 | A kind of preparation method and application of spine date seed oil microcapsules and oral solid formulation |
-
2003
- 2003-09-10 CN CNA031345581A patent/CN1491693A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229247B (en) * | 2007-12-28 | 2011-06-01 | 重庆理工大学 | Medicine preparation for treating insomnia and preparing method thereof |
| CN102258192A (en) * | 2011-07-11 | 2011-11-30 | 王跃进 | Enhanced red date soft capsule nutrition |
| CN102258192B (en) * | 2011-07-11 | 2012-12-12 | 王跃进 | Enhanced red date soft capsule nutrition |
| CN103039962A (en) * | 2011-10-15 | 2013-04-17 | 北京以岭药业有限公司 | Jujube seed oil soft capsule and preparation method thereof |
| CN103039962B (en) * | 2011-10-15 | 2016-12-14 | 北京以岭药业有限公司 | A kind of Semen Ziziphi Spinosae oil soft capsule and preparation method thereof |
| CN104886568A (en) * | 2015-05-13 | 2015-09-09 | 中国中轻国际工程有限公司 | Wild jujube seed oil soft capsule production technology |
| CN105106347A (en) * | 2015-06-26 | 2015-12-02 | 重庆医科大学 | Semen ziziphi spinosae soft capsules and preparation method thereof |
| CN105286013A (en) * | 2015-09-23 | 2016-02-03 | 安徽唐人药业有限公司 | Jujube kernel essential oil soft capsule and making method |
| CN105477100A (en) * | 2015-12-23 | 2016-04-13 | 无锡瑞盈生命科学有限公司 | Lucid ganoderma spore oil compound health care spray and preparation method |
| WO2018045547A1 (en) * | 2016-09-09 | 2018-03-15 | 石家庄以岭药业股份有限公司 | Applications of jujube seed oil in treating medicinal insomnia |
| US10881704B2 (en) | 2016-09-09 | 2021-01-05 | Shijiazhuang Yiling Pharmaceutical Co., Ltd. | Usage of semen Ziziphi spinosae oil in the treatment of medicinal insomnia |
| CN110419596A (en) * | 2019-08-21 | 2019-11-08 | 天津国际生物医药联合研究院 | A kind of preparation method and application of spine date seed oil microcapsules and oral solid formulation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1628786A (en) | Medicine for treating hyperlipemia | |
| CN1491693A (en) | Extraction of wild jujube seed oil and preparation of soft capsule and function on central nervous system | |
| CN1304039C (en) | Chinese medicine composition with functions of reducing blood-pressure, reducing-fat, anti-dizzy and calming wind, its preparing method and use | |
| CN1883638A (en) | Compound medicine for treating depression and method for preparing same | |
| CN1857654A (en) | Trachaitis treating preparation and its preparing process | |
| CN1557842A (en) | Process for extracting polygonatum polysaccharides, preparing process for medical preparation and use thereof | |
| CN1872278A (en) | A composition of medication | |
| CN1628662A (en) | Medicine with abirritation | |
| CN1256090C (en) | Application in antidepressants preparation of asiatic acid and derivation | |
| CN1679648A (en) | Mailuoning injection and its preparation and quality control | |
| CN1720948A (en) | Dripping pills of lllicium henryi dripping pills and method for preparing the same | |
| CN1259057C (en) | Pharmaceutical composition containing ginkgo leaf poly pentenol and its preparing method | |
| CN1452973A (en) | Orally taken antioxidant and antilipemic medicine | |
| CN1616060A (en) | Chinese medicine drippling pill preparation for promoting blood circulation and removing blood stasis, promoting Qi circulation and rilieving pain | |
| CN1714811A (en) | Radix bupleuri dripping pill and its preparing method | |
| CN1301099C (en) | Earthworm drip pill and its preparation method | |
| CN1686302A (en) | Traditional Chinese medicine for treating non-alcoholic simple fatty liver and its preparation method | |
| CN1772122A (en) | Indian stringbush prepn with antiphlogistic and detoxicating functions | |
| CN1287800C (en) | Medicine for regulating nerve system, treating epilepsia disease | |
| CN1179735C (en) | Litholytic medicine for treating hepatolith and preparation process thereof | |
| CN1205982C (en) | Xiangdan drop liquid for treating angiocardiopathy | |
| CN1733189A (en) | Technique for preparing Yueju capsule and quality control method | |
| CN1563308A (en) | Antianxity effect of egg of Rana Cnensinensis and preparation method | |
| CN1679793A (en) | Xiaoaiping preparation against cancers and its making method | |
| CN1634481A (en) | Honeysuckle flower soft capsule and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |