CN103977354A - Chinese medicinal extract with anti-depression effect and preparation method and application thereof - Google Patents
Chinese medicinal extract with anti-depression effect and preparation method and application thereof Download PDFInfo
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Abstract
The invention aims to provide a Chinese medicinal extract with an anti-depression effect and a preparation method and application thereof. The Chinese medicinal composition is screened from Chinese thorowax root-turmeric root-tuber prescription medicaments based on an anti-depression medicament system, and phenol components and terpene components in a Chinese thorowax root-turmeric root-tuber prescription are obtained by means of steam distillation, ethanol extraction and porous adsorption resin purification enrichment. As proved by a pharmacological experiment, the medicinal composition can be used for improving the depressive behavior of a model mouse, shortening the standing time of the mouse and restraining the body temperature drop caused by reserpine, thereby preventing and treating depression.
Description
Technical field
The invention belongs to drug development research field, relate to a kind of drug substance, particularly a kind of drug substance with antidepressant activity and preparation method thereof.
Background technology
Depression claims again depressive disorder, and the remarkable and lasting mental state of take is low is main clinical characteristics, is the main Types of mood disorders.The traditional Chinese medical science thinks that melancholia is many by do not relax depression and stagnation of QI and causing a disease of feelings will, take feel depressed, irritable emotion, chest expire vexed, distending pain over the hypochondrium or irritability is wanted to cry or swallow in if any foreign body, the disease such as to block be cardinal symptom.< < Plain Questions is hexa-atomic, and the large opinion > > that just recording says: " strongly fragrant very person control how? soothing the stagnant liver, dispersing fire for treating depression of fire, dampness accumulated in the spleen should be removed, ventilating the obstructed lung-QI for relieving the depression of the lung, retention of fluid being treated with draining method." doctor trained in Western medicine is still not fully aware of to the definite pathophysiological mechanism of depression morbidity at present, although some Western medicine are as selective serotonin reuptake inhibitor (SSRI, represent medicine fluoxetine, paroxetine, Sertraline etc.), 5-hydroxy tryptamine and NRI (SNRI, represent medicine venlafaxine and duloxetine), norepinephrine and specificity 5-hydroxy tryptamine energy antidepressants (NaSSA, represent medicine mirtazapine) aspect alleviate depression, obtain larger progress, but be only symptomatic treatment, can not effect a radical cure, and, these symptomatic treatments are not all effective to all depressive patients, and untoward reaction is larger.Treatment by Chinese herbs depression has that toxic and side effects is little, the obvious feature of therapeutic effect.
The present invention be take the scorching academician's of Wang Yong bavin gold side, clinical experience side as just former, exploration discovery a kind of Chinese medicine combinations of substances with antidepressant effect, and to take type composition and the index composition of drug effect association be comprehensive consideration, set up reliable and stable, preparation technology and scientific comprehensive method of quality control when being applicable to actual production, be conducive to the research and development of further original new drug.At present, have no the relevant report of purification antidepressant drug combinations of substances from bavin gold side, also have no the correlational study report of relevant said composition aspect treatment depressive illness.
Summary of the invention
Another object of the present invention is to provide a kind of prescription former combination, Radix Bupleuri, Radix Curcumae, Herba Eupatorii, Radix Polygoni Multiflori Preparata, Cortex Cinnamomi etc., consists of.
The object of the present invention is to provide a kind of drug substance combination with antidepressant effect, its drug system is mainly comprised of phenols, terpenoid.
Another object of the present invention is to provide its preparation method, and the 3rd object of the present invention is to provide its application at anti-depression aspect, and the 4th object of the present invention is to provide its quality testing and control method thereof.
The 4th object of the present invention is to provide its antidepressant activity.The 5th object of the present invention is to provide the goods of this Chinese medicine composition of matter and in the application of medicine, field of food.
The object of the invention is to realize by following approach:
Chinese medicine combinations of substances of the present invention can and substitute kind by following 4 groups of medicinal plants, comprises its medicinal part and dis-medicinal part, and medical material and decoction pieces combination thereof are made.
Group 1: samphire and the processed products thereof such as Radix Bupleuri, Radix Bupleuri, Radix Bupleuri Scorzonerifolii, bigleaf thorowax root, Radix Bupeuri Scorzonerfolii., Radix Bupleuri (processed with vinegar).
Group 2: the zingiberaceous plants such as Radix Curcumae, RADIX CURCUMAE, yellow silk Radix Curcumae, osmanthus Radix Curcumae, green filament Radix Curcumae.
Group 3: the equal or congener of the Compositae Eupatoriums such as Herba Eupatorii, Herba Chlorophyti, water perfume (or spice).
Group 4: the polygonaceae plants such as Radix Polygoni Multiflori, Caulis Polygoni Multiflori and processed product thereof.
Group 5: Cortex Cinnamomi, CORTEX CINNAMOMI, plate osmanthus, Cortex Cinnamomi, osmanthus are logical, Cortex Cinnamomi, broken, the high Cortex Cinnamomi Bejolghotae in osmanthus, low Cortex Cinnamomi Bejolghotae cinnamon and processed product thereof.
Chinese medicine combinations of substances of the present invention, can be after above-mentioned raw materials medicine combination with ethanol or other alcohols, rare alcohol or other organic solvents or water extraction again by macroporous adsorbent resin or other chromatographic processes, as polyamide chromatography etc., or the purification such as solvent extraction obtains.
Chinese medicine combinations of substances of the present invention can be by the extract of above-mentioned raw materials medicine after further enriching and purifying or the macroporous resin prepared product of above-mentioned raw materials medicine mix.
Chinese medicine combinations of substances of the present invention can be through chemosynthesis or structural modification, and biosynthesis or biology the approach such as turn and obtain.
Chinese medicine combination of the present invention is preferably made by following crude drug:
Radix Bupleuri 100-300 weight portion Radix Curcumae 100-300 weight portion
Herba Eupatorii 100-300 weight portion Radix Polygoni Multiflori Preparata 100-500 weight portion
Cortex Cinnamomi 1-200 weight portion
The preparation method of drug substance of the present invention comprises the steps:
Step 1: choose above-mentioned raw materials medicine;
Step 2: vapor distillation;
Step 3: ethanol extraction;
Step 4: purification with macroreticular resin;
In above-mentioned steps 2, by above-mentioned raw materials medicine (except Radix Polygoni Multiflori Preparata) vapor distillation, 5-10 times of solvent extraction 1-10h.
In above-mentioned steps 3, by step 2 Raw medicine and Radix Polygoni Multiflori Preparata 10-80% alcohol reflux 1-3 time, extract 0.5-2.5 hour at every turn; Extract obtainedly add aqueous dispersion and dissolve, making concentration of aqueous solution is 0.01-0.1g/mL.
In above-mentioned steps 4, by low pole or polar macroporous adsorption resin, absorption flow velocity is 1-5BV/h, resin column blade diameter length ratio is 1: 4-10, sample solution concentration is 0.02-0.1g/mL, and water elution 1-5 times of resin volume carries out remove impurity, and water remove impurity flow velocity is 1-5BV/h, 3-10 times of resin volume of 10-60% ethanol elution, elution flow rate is 1-5BV/h, collects ethanol elution, reclaims solvent, drying under reduced pressure, obtains phenols and terpenoid active component.
In this Chinese medicine extract, terpenoid content is 0.5-1.5%, and wherein saikoside b2 content is 0.01%～0.6%, and phenols content is 5-20%, and preferably total phenol content is 10-20%.
To be extract obtained above, and add conventional adjuvant, preparation process be routinely made the acceptable any conventional dosage form of pharmaceutics, comprises capsule, tablet, granule, gel, slow releasing agent, oral liquid, drop pill.
Chinese medicine extract of the present invention is obtained through vapor distillation, ethanol extraction, purification with macroreticular resin by Chai Jinfang, enrichment phenols component and the ter penoids in Chai Jinfang, simultaneously through copying depression model mice evidence, Chinese medicine extract of the present invention can improve the Depressive behavior of model mice, shorten the mice dead time, suppress the body temperature reduction that reserpine causes.
Below principle of the present invention and feature are described, example, only for explaining the present invention, is not intended to limit scope of the present invention.
Experimental example 1 antidepressant activity of the present invention position causes the improvement effect of depression model mice to reserpine antagonism
(1) experiment material
1. laboratory animal
1.1 laboratory animal
Healthy ICR mice (female, male), body weight 18-20g, is provided by Si Beifu (Beijing) Animal Science company limited.Credit number: SCXK (capital) 2012-0001.
2. medicine and reagent
Be subject to reagent: antidepressant activity position, bavin gold side, by embodiment 6 method preparations, before administration, use water dissolution wiring solution-forming.
Fluoxetine Hydrochloride (Lilly Co., Eli., lot number 0745A) mice dosage is 3.33/kg.
(2) experimental technique and result
1. grouping and administration
Rat is divided into 4 groups at random by body weight, blank group, model group, positive controls (fluoxetine Hydrochloride), prepared product group, ethanol extract group and water extract group, and 10 every group, successive administration 7 days, model group and normal group give isometric water.
2. experimental technique
The experiment of mice forced swimming: after the 6th administration 60min, carry out the experiment of mice forced swimming, mice is put into high 20cm, in the beaker of internal diameter 15cm, one, every cylinder, depth of water 15cm in cylinder, 25 ± 1 ℃ of water temperatures.After mice swimming 2min, start immediately to observe, observe and continue 4min, measure the 4min dead time (6min altogether), (mice stops struggling in water, or animal is floating state, only the has tiny limb motion) time.
Tail suspension test: after the 6th administration 60min, carry out tail suspension test experiment.Mouse tail, apart from the about 1cm of end place's immobilization with adhesive tape, is made to mice reversal of the natural order of things, and its head is from the about 10cm of desktop.Mice hangs after 2min, gets started observation, observes and continues 4min, and record not when mice is movable, occurs when motionless starting stopwatch, in accumulative total 6min after motionless (mice aloft stops struggling, or only has tiny limb motion) time of mice of 4min.
Reserpine antagonistic experiment: before last administration, except blank group, injection reserpine 4mg/kg.After 1h, mice is holded up, in observation experiment animal 2min, blepharoptosis situation, according to the scoring of blepharoptosis situation, standards of grading are: it is 1 minute that eye closes 1/4, and it is 2 minutes that eye closes 2/4, and it is 3 minutes that eye closes 3/4, and full cut-off is 4 minutes; After 2h, measure mice anus temperature.
3. statistical analysis: adopt spss17.0 software to analyze, experimental result represents with mean ± standard error.Respectively each is organized to administration mice and model group mice and normal group mice and compare, try to achieve group difference.When α < 0.05, judge significance difference opposite sex statistical method
4. experimental result
Table 1 is respectively organized the impact of medicine on mice behavior
Dead time (swimming, outstanding tail): with normal group comparison, P < 0.05 use * represents, P < 0.01 use * * represents
The score of sagging situation, anus temperature: with model group comparison, P < 0.05 use * represents, P < 0.01 use * * represents
(3) conclusion
Compare with model group, the anti-silly depressibility prepared product in bavin gold side, ethanol extract, water extract all can improve the Depressive behavior of model mice, and the model mice dead time is shortened, and suppress the body temperature reduction that reserpine causes.Compare, prepared product dose is minimum, and drug effect is best.
following embodiment all can realize the effect of above-mentioned experimental example.The specific embodiments of lifting only for explaining the present invention, and
non-for limiting scope of the present invention.
The specific embodiment
Embodiment 1: capsule
Radix Bupleuri 100g Radix Curcumae 100g
Herba Eupatorii 100g Radix Polygoni Multiflori Preparata 150g
Cortex Cinnamomi 15g
Get according to the above ratio crude drug decoction pieces 1kg, all the other decoction pieces vapor distillations except Radix Polygoni Multiflori Preparata, 9 times of water extraction 5h.After medical material merges, with 70% alcohol reflux 2 times, each 1.5 hours; Extract obtainedly add aqueous dispersion and dissolve, making concentration of aqueous solution is 0.01-0.1g/mL, and preferably making concentration of aqueous solution is 0.02-0.025g/mL; (to roll over raw medicinal herbs amount, wherein phenols concentration is 0.7546mg/ml, and terpenoid concentration is 0.2012mg/ml).
By DM-130 type macroporous adsorbent resin, absorption flow velocity 2BV/h, resin column blade diameter length ratio is 1: 6, sample solution concentration is 0.02-0.025g/mL, 1 times of resin volume of water elution carries out remove impurity, remove impurity flow velocity is 2BV/h, 30-40% ethanol and 60-70% ethanol elution 4-5BV resin volume, and elution flow rate is 2BV/h, collect ethanol elution, reclaim solvent, drying under reduced pressure, obtains.Add conventional adjuvant, according to common process, make capsule;
The content assaying method of terpenoid:
Reference substance: saikoside b2;
Assay method: chromatographic column: Waters Xbridge Shield RP18 (4.6 * 250mm, 5 μ m); Mobile phase is acetonitrile (A)-0.1% (B) aqueous formic acid; Condition of gradient elution is in Table 3-2-1,30 ℃ of column temperatures; Detect wavelength 190-800nm; Flow velocity 1.0mL/min;
Table 2 eluent gradient elution requirement
In bavin gold side prepared product, ter penoids content reaches 1.4% after measured, and saikoside b2 reaches 0.6%;
Phenols content assaying method:
Reference substance: stilbene glucoside;
Reagent: 0.6% liquor ferri trichloridi, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
Coloration method: the accurate sample solution of drawing is in right amount in the brown volumetric flask of 25ml, add 70% methanol to 5ml, add again 0.3% sodium dodecyl sulfate solution 1.6ml, and 0.6% ferric chloride-0.9% potassium ferricyanide mixed solution 2.4ml of 1: 1,7min is placed in dark place, with 0.1mol/L hydrochloric acid, adds to 25ml graduation mark, shakes up, 30min is placed in dark place, in order to measuring;
Assay method: sample after above-mentioned colour developing is measured in 766 ± 2nm wave-length coverage, recorded its maximum absorbance value, phenols content reaches 12% after measured.
Embodiment 2: tablet
Radix Bupleuri 100g Radix Curcumae 80g
Herba Eupatorii 100g Radix Polygoni Multiflori Preparata 100g
Cortex Cinnamomi 10g
Get according to the above ratio crude drug decoction pieces 1kg, all the other decoction pieces vapor distillations except Radix Polygoni Multiflori Preparata, 7 times of water extraction 4h.After medical material merges, with 70% alcohol reflux 3 times, each 1.5 hours; Extract obtainedly add aqueous dispersion and dissolve, making concentration of aqueous solution is 0.01-0.1g/mL, and preferably making concentration of aqueous solution is 0.02-0.025g/mL; (to roll over raw medicinal herbs amount, wherein phenols concentration is 0.7546mg/ml, and terpenoid concentration is 0.2012mg/ml).
By DM-130 type macroporous adsorbent resin, absorption flow velocity 2BV/h, resin column blade diameter length ratio is 1: 6, sample solution concentration is 0.02-0.025g/mL, 1 times of resin volume of water elution carries out remove impurity, remove impurity flow velocity is 2BV/h, 30-40% ethanol and 60-70% ethanol elution 4-5BV resin volume, and elution flow rate is 3BV/h, collect ethanol elution, reclaim solvent, drying under reduced pressure, obtains.Add conventional adjuvant, according to common process, make tablet;
The content assaying method of terpenoid:
Reference substance: saikoside b2;
Assay method: chromatographic column: Waters Xbridge Shield RP18 (4.6 * 250mm, 5 μ m); Mobile phase is acetonitrile (A)-0.1% (B) aqueous formic acid; Condition of gradient elution is in Table 3-2-1,30 ℃ of column temperatures; Detect wavelength 190-800nm; Flow velocity 1.0mL/min;
Table 2 eluent gradient elution requirement
In bavin gold side prepared product, ter penoids content reaches 1.4% after measured, and saikoside b2 reaches 0.6%;
Phenols content assaying method:
Reference substance: stilbene glucoside;
Reagent: 0.6% liquor ferri trichloridi, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
Coloration method: the accurate sample solution of drawing is in right amount in the brown volumetric flask of 25ml, add 70% methanol to 5ml, add again 0.3% sodium dodecyl sulfate solution 1.6ml, and 0.6% ferric chloride-0.9% potassium ferricyanide mixed solution 2.4ml of 1: 1,7min is placed in dark place, with 0.1mol/L hydrochloric acid, adds to 25ml graduation mark, shakes up, 30min is placed in dark place, in order to measuring;
Assay method: sample after above-mentioned colour developing is measured in 766 ± 2nm wave-length coverage, recorded its maximum absorbance value, phenols content reaches 12% after measured.
Embodiment 3: pill
Radix Bupleuri 80g Radix Curcumae 80g
Herba Eupatorii 100g Radix Polygoni Multiflori Preparata 150g
Cortex Cinnamomi 15g
Get according to the above ratio crude drug decoction pieces 1kg, all the other decoction pieces vapor distillations except Radix Polygoni Multiflori Preparata, 5 times of water extraction 3h.After medical material merges, with 50% alcohol reflux 2 times, each 2 hours; Extract obtainedly add aqueous dispersion and dissolve, making concentration of aqueous solution is 0.01-0.1g/mL, and preferably making concentration of aqueous solution is 0.02-0.025g/mL; (to roll over raw medicinal herbs amount, wherein phenols concentration is 0.7546mg/ml, and terpenoid concentration is 0.2012mg/ml).
By DM-130 type macroporous adsorbent resin, absorption flow velocity 3BV/h, resin column blade diameter length ratio is 1: 8, sample solution concentration is 0.02-0.025g/mL, 1 times of resin volume of water elution carries out remove impurity, remove impurity flow velocity is 2BV/h, 30-40% ethanol and 60-70% ethanol elution 4-5BV resin volume, and elution flow rate is 2BV/h, collect ethanol elution, reclaim solvent, drying under reduced pressure, obtains.Add conventional adjuvant, according to common process, make pill;
The content assaying method of terpenoid:
Reference substance: saikoside b2;
Assay method: chromatographic column: Waters Xbridge Shield RP18 (4.6 * 250mm, 5 μ m); Mobile phase is acetonitrile (A)-0.1% (B) aqueous formic acid; Condition of gradient elution is in Table 3-2-1,30 ℃ of column temperatures; Detect wavelength 190-800nm; Flow velocity 1.0mL/min;
Table 2 eluent gradient elution requirement
In bavin gold side prepared product, ter penoids content reaches 1.4% after measured, and saikoside b2 reaches 0.6%;
Phenols content assaying method:
Reference substance: stilbene glucoside;
Reagent: 0.6% liquor ferri trichloridi, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
Coloration method: the accurate sample solution of drawing is in right amount in the brown volumetric flask of 25ml, add 70% methanol to 5ml, add again 0.3% sodium dodecyl sulfate solution 1.6ml, and 0.6% ferric chloride-0.9% potassium ferricyanide mixed solution 2.4ml of 1: 1,7min is placed in dark place, with 0.1mol/L hydrochloric acid, adds to 25ml graduation mark, shakes up, 30min is placed in dark place, in order to measuring;
Assay method: sample after above-mentioned colour developing is measured in 766 ± 2nm wave-length coverage, recorded its maximum absorbance value, phenols content reaches 12% after measured.
Embodiment 4: oral liquid
Radix Bupleuri 100g Radix Curcumae 100g
Herba Eupatorii 80g Radix Polygoni Multiflori Preparata 120g
Cortex Cinnamomi 10g
Get according to the above ratio crude drug decoction pieces 1kg, all the other decoction pieces vapor distillations except Radix Polygoni Multiflori Preparata, 6 times of water extraction 4h.After medical material merges, with 70% alcohol reflux 3 times, each 1 hour; Extract obtainedly add aqueous dispersion and dissolve, making concentration of aqueous solution is 0.01-0.1g/mL, and preferably making concentration of aqueous solution is 0.02-0.025g/mL; (to roll over raw medicinal herbs amount, wherein phenols concentration is 0.7546mg/ml, and terpenoid concentration is 0.2012mg/ml).
By DM-130 type macroporous adsorbent resin, absorption flow velocity 3BV/h, resin column blade diameter length ratio is 1: 6, sample solution concentration is 0.02-0.025g/mL, 1 times of resin volume of water elution carries out remove impurity, remove impurity flow velocity is 3BV/h, 30-40% ethanol and 60-70% ethanol elution 4-5BV resin volume, and elution flow rate is 2BV/h, collect ethanol elution, reclaim solvent, drying under reduced pressure, obtains.Add conventional adjuvant, according to common process, make oral liquid;
The content assaying method of terpenoid:
Reference substance: saikoside b2;
Assay method: chromatographic column: Waters Xbridge Shield RP18 (4.6 * 250mm, 5 μ m); Mobile phase is acetonitrile (A)-0.1% (B) aqueous formic acid; Condition of gradient elution is in Table 3-2-1,30 ℃ of column temperatures; Detect wavelength 190-800nm; Flow velocity 1.0mL/min;
Table 2 eluent gradient elution requirement
In bavin gold side prepared product, ter penoids content reaches 1.4% after measured, and saikoside b2 reaches 0.6%;
Phenols content assaying method:
Reference substance: stilbene glucoside;
Reagent: 0.6% liquor ferri trichloridi, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
Coloration method: the accurate sample solution of drawing is in right amount in the brown volumetric flask of 25ml, add 70% methanol to 5ml, add again 0.3% sodium dodecyl sulfate solution 1.6ml, and 0.6% ferric chloride-0.9% potassium ferricyanide mixed solution 2.4ml of 1: 1,7min is placed in dark place, with 0.1mol/L hydrochloric acid, adds to 25ml graduation mark, shakes up, 30min is placed in dark place, in order to measuring;
Assay method: sample after above-mentioned colour developing is measured in 766 ± 2nm wave-length coverage, recorded its maximum absorbance value, phenols content reaches 12% after measured.
Embodiment 5: injection
Radix Bupleuri 100g Radix Curcumae 100g
Herba Eupatorii 100g Radix Polygoni Multiflori Preparata 100g
Cortex Cinnamomi 15g
Get according to the above ratio crude drug decoction pieces 1kg, all the other decoction pieces vapor distillations except Radix Polygoni Multiflori Preparata, 7 times of water extraction 6h.After medical material merges, with 40% alcohol reflux 1 time, each 1.5 hours; Extract obtainedly add aqueous dispersion and dissolve, making concentration of aqueous solution is 0.01-0.1g/mL, and preferably making concentration of aqueous solution is 0.02-0.025g/mL; (to roll over raw medicinal herbs amount, wherein phenols concentration is 0.7546mg/ml, and terpenoid concentration is 0.2012mg/ml).
By DM-130 type macroporous adsorbent resin, absorption flow velocity 1BV/h, resin column blade diameter length ratio is 1: 8, sample solution concentration is 0.02-0.025g/mL, 2 times of resin volumes of water elution carry out remove impurity, remove impurity flow velocity is 1BV/h, 30-40% ethanol and 60-70% ethanol elution 4-5BV resin volume, and elution flow rate is 3BV/h, collect ethanol elution, reclaim solvent, drying under reduced pressure, obtains.Add conventional adjuvant, according to common process, make injection;
The content assaying method of terpenoid:
Reference substance: saikoside b2;
Assay method: chromatographic column: Waters Xbridge Shield RP18 (4.6 * 250mm, 5 μ m); Mobile phase is acetonitrile (A)-0.1% (B) aqueous formic acid; Condition of gradient elution is in Table 3-2-1,30 ℃ of column temperatures; Detect wavelength 190-800nm; Flow velocity 1.0mL/min;
Table 2 eluent gradient elution requirement
In bavin gold side prepared product, ter penoids content reaches 1.4% after measured, and saikoside b2 reaches 0.6%;
Phenols content assaying method:
Reference substance: stilbene glucoside;
Reagent: 0.6% liquor ferri trichloridi, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
Coloration method: the accurate sample solution of drawing is in right amount in the brown volumetric flask of 25ml, add 70% methanol to 5ml, add again 0.3% sodium dodecyl sulfate solution 1.6ml, and 0.6% ferric chloride-0.9% potassium ferricyanide mixed solution 2.4ml of 1: 1,7min is placed in dark place, with 0.1mol/L hydrochloric acid, adds to 25ml graduation mark, shakes up, 30min is placed in dark place, in order to measuring;
Assay method: sample after above-mentioned colour developing is measured in 766 ± 2nm wave-length coverage, recorded its maximum absorbance value, phenols content reaches 12% after measured.
Embodiment 6:
Radix Bupleuri 100g Radix Curcumae 100g
Herba Eupatorii 100g Radix Polygoni Multiflori Preparata 150g
Cortex Cinnamomi 15g
Get according to the above ratio crude drug decoction pieces 1kg, all the other decoction pieces vapor distillations except Radix Polygoni Multiflori Preparata, 7 times of water extraction 4h.After medical material merges, with 70% alcohol reflux 2 times, each 1.5 hours; Extract obtainedly add aqueous dispersion and dissolve, making concentration of aqueous solution is 0.01-0.1g/mL, and preferably making concentration of aqueous solution is 0.02-0.025g/mL; (to roll over raw medicinal herbs amount, wherein phenols concentration is 0.7546mg/ml, and terpenoid concentration is 0.2012mg/ml).
By DM-130 type macroporous adsorbent resin, absorption flow velocity 3BV/h, resin column blade diameter length ratio is 1: 6, sample solution concentration is 0.02-0.025g/mL, 2 times of resin volumes of water elution carry out remove impurity, remove impurity flow velocity is 2BV/h, 30-40% ethanol and 60-70% ethanol elution 4-5BV resin volume, and elution flow rate is 3BV/h, collect ethanol elution, reclaim solvent, drying under reduced pressure, is Chinese medicine extract of the present invention;
The content assaying method of terpenoid:
Reference substance: saikoside b2;
Assay method: chromatographic column: Waters Xbridge Shield RP18 (4.6 * 250mm, 5 μ m); Mobile phase is acetonitrile (A)-0.1% (B) aqueous formic acid; Condition of gradient elution is in Table 3-2-1,30 ℃ of column temperatures; Detect wavelength 190-800nm; Flow velocity 1.0mL/min;
Table 2 eluent gradient elution requirement
In bavin gold side prepared product, ter penoids content reaches 1.4% after measured, and saikoside b2 reaches 0.6%;
Phenols content assaying method:
Reference substance: stilbene glucoside;
Reagent: 0.6% liquor ferri trichloridi, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
Coloration method: the accurate sample solution of drawing is in right amount in the brown volumetric flask of 25ml, add 70% methanol to 5ml, add again 0.3% sodium dodecyl sulfate solution 1.6ml, and 0.6% ferric chloride-0.9% potassium ferricyanide mixed solution 2.4ml of 1: 1,7min is placed in dark place, with 0.1mol/L hydrochloric acid, adds to 25ml graduation mark, shakes up, 30min is placed in dark place, in order to measuring;
Assay method: sample after above-mentioned colour developing is measured in 766 ± 2nm wave-length coverage, recorded its maximum absorbance value, phenols content reaches 12% after measured.
Embodiment 7: the preparation of capsule
Get Chinese medicine combinations of substances 200g of the present invention, pulverize, cross 80 mesh sieves, 100g is mixed homogeneously with microcrystalline Cellulose, with 95% alcohol granulation, dry, with 20 mesh sieve granulate, fill capsule.
Embodiment 8: the preparation of tablet
Get Chinese medicine combinations of substances 50g of the present invention, pulverize, cross 80 mesh sieves, mix homogeneously with microcrystalline Cellulose 70g, carboxymethyl starch sodium 5g, with 5%PVP, granulate, dry, with 20 mesh sieve granulate, add magnesium stearate 2g, tabletting.
Embodiment 9: the preparation of drop pill
Get Chinese medicine combinations of substances 60g of the present invention, pulverize, cross 80 mesh sieves, mix homogeneously, drop in the polyethylene glycol 6000 of 180g heating and melting, be stirred to dissolving, be transferred in reservoir, airtight and insulation at 80～90 ℃, regulate pill dripping machine drop quantitative valve, splash into from top to bottom in the liquid paraffin of 10～15 ℃, the drop pill of formation is drained and erasing liquor paraffin body, dry.
Embodiment 10: the preparation of oral liquid
Get Chinese medicine combinations of substances 70g of the present invention, pulverize, cross 80 mesh sieves, mix homogeneously, mix with Mel 1000g, sucrose 200g, sodium benzoate 10g and distilled water 2000ml, be heated to 85～90 ℃, be stirred to dissolve, insulation 30min, filter, filtrate is diluted with water to 4000ml, stirs, embedding, sterilizing.
Embodiment 11: the preparation of injection
Get Chinese medicine combinations of substances 100g of the present invention, inject water and make in right amount to dissolve, 0.02% the active carbon that adds configuration amount stirs 5～10min, filters, filtrate is diluted to 10L left and right, adds sodium chloride and regulates osmotic pressure to ooze to waiting, and regulates pH7.5～8.0, ultrafiltration, embedding, 100 ℃ of sterilizing 30min.
Embodiment 12: the preparation of injectable powder
Get Chinese medicine combinations of substances 100g of the present invention, inject water and dilute sodium hydroxide and make in right amount to dissolve, 0.02% the raw charcoal of living that adds configuration amount stirs 5～10min, filter, filtrate is diluted to 1L, regulates pH6.5～7.8, ultrafiltration, spraying is dry, and dry powder is aseptic subpackaged.Every 100mg, injects before use water and makes in right amount to dissolve, with slowly intravenous drip after sodium chloride transfusion 250～500ml dilution.
Claims (12)
1. have antidepressant effect a Chinese medicine combinations of substances, it is characterized in that the preparation method of this Chinese medicine combinations of substances comprises the steps:
Step 1: choose crude drug;
Step 2: vapor distillation;
Step 3: ethanol extraction;
Step 4: purification with macroreticular resin;
This Chinese medicine combinations of substances consists of two parts, and first is phenols, and wherein phenols content is 7-20%, second portion terpenoid, and wherein terpenoid content is 1-5%, wherein saikoside b2 content is 0.01%～0.6%.
2. Chinese medicine extract as claimed in claim 1, is characterized in that consisting of of step 1 Raw medicine:
Radix Bupleuri 100-300 weight portion Radix Curcumae 100-300 weight portion
Herba Eupatorii 100-300 weight portion Radix Polygoni Multiflori Preparata 100-500 weight portion
Cortex Cinnamomi 1-200 weight portion
3. Chinese medicine extract as claimed in claim 1 or 2, is characterized in that in step 2, by crude drug 10-80% alcohol reflux 2-4 time, extracts 0.5-2 hour at every turn.
4. Chinese medicine extract as claimed in claim 1 or 2, is characterized in that in step 3, adds aqueous dispersion and dissolves step 2 is extract obtained, and making concentration of aqueous solution is 0.02-0.1g/mL.
5. Chinese medicine extract as claimed in claim 1 or 2, it is characterized in that in step 3, aqueous dispersions is by low pole or nonpolar macroporous adsorption resin, absorption flow velocity is 1-5BV/h, resin column blade diameter length ratio is 1: 4-10, sample solution concentration is 0.02-0.1g/mL, water elution 1-5 times of resin volume carries out remove impurity, water remove impurity flow velocity is 1-5BV/h, 3-10 times of resin volume of 10-60% ethanol elution, and elution flow rate is 1-5BV/h, collect ethanol elution, reclaim solvent, drying under reduced pressure, obtains phenols and terpenoid active component.
6. as described in right 1-5, Chinese medicine combinations of substances is characterized in that and substituting kind by following 5 groups of medicinal plants, comprises its medicinal part and dis-medicinal part, and medical material and decoction pieces combination thereof are made:
Group 1: samphire and the processed products thereof such as Radix Bupleuri, Radix Bupleuri, Radix Bupleuri Scorzonerifolii, bigleaf thorowax root, Radix Bupeuri Scorzonerfolii., Radix Bupleuri (processed with vinegar).
Group 2: zingiberaceous plant and the processed products thereof such as Radix Curcumae, RADIX CURCUMAE, yellow silk Radix Curcumae, osmanthus Radix Curcumae, green filament Radix Curcumae.
Group 3: the Compositae Eupatoriums such as Herba Eupatorii, Herba Chlorophyti, water perfume (or spice) equal or congener and processed product thereof.
Group 4: the polygonaceae plants such as Radix Polygoni Multiflori, Caulis Polygoni Multiflori and processed product thereof.
Group 5: Cortex Cinnamomi, CORTEX CINNAMOMI, plate osmanthus, Cortex Cinnamomi, osmanthus are logical, Cortex Cinnamomi, broken, the high Cortex Cinnamomi Bejolghotae in osmanthus, low Cortex Cinnamomi Bejolghotae cinnamon and processed product thereof.
As described in right 1-5 Chinese medicine combinations of substances it is characterized in that can be after above-mentioned raw materials medicine combination with ethanol or other alcohols, rare alcohol or other organic solvents or water extraction again by macroporous adsorbent resin or other chromatographic processes, as polyamide chromatography etc., or the purification such as solvent extraction obtains.
As described in right 1-5 Chinese medicine combinations of substances it is characterized in that can be by the extract of crude drug described in right 6 after further enriching and purifying or the macroporous resin prepared product of above-mentioned raw materials medicine mix.
As described in right 1-5 Chinese medicine combinations of substances it is characterized in that can be through chemosynthesis or structural modification, biosynthesis or biology the approach such as turn and obtain.
10. Chinese medicine combinations of substances as described in claim 1-9, it is characterized in that adding various pharmaceutic adjuvant well known in the art, preparation process is routinely made the acceptable any conventional dosage form of pharmaceutics, also can be made into other transmission system drug-delivery preparations such as long-acting and slow releasing preparation, controlled release preparation, targeting preparation.Obtained medicament can be used as people's medicine, veterinary drug, plant medication use or uses.
11. as described in claim 1-9 Chinese medicine combinations of substances, it is characterized in that adding known food additive to make health food or the beverage with prevention and health care function as antiseptic, antioxidant agent, coloring agent, thickening agent and stabilizing agent, bulking agent, sweeting agent, acidity agent, brightening agent, spice etc.
12. Chinese medicine combinations of substances as described in as arbitrary in claim 1-9 have the application in antidepressant drug in preparation.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110179809A (en) * | 2019-06-18 | 2019-08-30 | 山西大学 | Saikoside B2 is preparing the application in anti-depression drug |
| CN113057992A (en) * | 2021-04-23 | 2021-07-02 | 花安堂生物科技集团有限公司 | Application of tangerine extract in preparation of anti-depression product |
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2014
- 2014-05-27 CN CN201410229464.XA patent/CN103977354B/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110179809A (en) * | 2019-06-18 | 2019-08-30 | 山西大学 | Saikoside B2 is preparing the application in anti-depression drug |
| CN113057992A (en) * | 2021-04-23 | 2021-07-02 | 花安堂生物科技集团有限公司 | Application of tangerine extract in preparation of anti-depression product |
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| CN103977354B (en) | 2021-04-20 |
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