CN103977354B - Traditional Chinese medicine extract with anti-depression effect and preparation method and application thereof - Google Patents
Traditional Chinese medicine extract with anti-depression effect and preparation method and application thereof Download PDFInfo
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Abstract
The invention aims to provide a traditional Chinese medicine composition with an antidepressant effect and application thereof, the traditional Chinese medicine composition is prepared by screening bupleurum root prescription medicines based on an antidepressant system, phenolic components and terpenoid components in the bupleurum root prescription are obtained by subjecting the bupleurum root prescription to steam distillation, ethanol extraction and macroporous adsorption resin purification and enrichment, and meanwhile, pharmacodynamic experiments prove that the medicine composition can improve the depressive behavior of a model mouse, shorten the immobility time of the mouse and inhibit the body temperature reduction caused by reserpine, thereby preventing and treating depression.
Description
Technical Field
The invention belongs to the field of research and development of medicines, relates to a medicine substance, and particularly relates to a medicine substance with antidepressant activity and a preparation method thereof.
Background
Depression, also known as depressive disorder, is characterized clinically by a marked and persistent depression in the mood, the main type of mood disorder. The traditional Chinese medicine considers that the depression is mostly caused by depression of emotional depression and qi-soothing machine, and the main symptoms are depression of mood, restlessness of mood, chest fullness and oppression, hypochondriac distending pain, irritability and crying, foreign body obstruction in pharynx and the like. Su Wen, six-membered tribal grand treatise states that: what is treated by depression? Wooddepression, fire depression, earth depression, mental depression, water depression. Although the exact pathophysiological mechanism of depression onset in western medicine is not clear at present, some western medicines such as selective 5-hydroxytryptamine reuptake inhibitors (SSRI, which stands for the drugs fluoxetine, paroxetine, sertraline, etc.), 5-hydroxytryptamine and noradrenaline reuptake inhibitors (SNRI, which stands for the drugs venlafaxine and duloxetine), noradrenaline and specific 5-hydroxytryptamine antidepressants (NaSSA, which stands for the drug mirtazapine) make great progress in relieving depression, only symptomatic treatment and no radical treatment are available, and the symptomatic treatment is not effective for all depressed patients and has great adverse effects. The traditional Chinese medicine for treating depression has the characteristics of small toxic and side effects and obvious treatment effect.
The invention takes the clinical proved formula of the Wangyongyan academy as the source of the formula, explores and discovers a traditional Chinese medicine substance combination with the anti-depression effect, takes the type components and the index components related to the drug effect as the comprehensive consideration, establishes a stable and reliable preparation process and a scientific and comprehensive quality control method which are suitable for actual production and are simultaneously suitable for further innovation of the research and the development of the medicine. At present, no report related to the purification preparation of antidepressant drug substance combinations from the Chaikang prescription is found, and no report related to the research on the aspect of treating depression diseases of the composition is found.
Disclosure of Invention
The invention also aims to provide a traditional Chinese medicine formula composition which comprises radix bupleuri, radix curcumae, eupatorium, radix polygoni multiflori preparata, cinnamon and the like.
The invention aims to provide a medicinal substance composition with an antidepressant effect, wherein a medicinal system of the medicinal substance composition mainly comprises phenols and terpenoids.
The invention also provides a preparation method thereof, a third purpose of the invention is to provide the application of the invention in antidepressant, and a fourth purpose of the invention is to provide the quality detection and the control method thereof.
The fourth object of the present invention is to provide antidepressant activity thereof. The fifth purpose of the invention is to provide a product of the traditional Chinese medicine substance composition and application thereof in the fields of medicines and foods.
The purpose of the invention is realized by the following ways:
the Chinese medicinal material composition can be prepared from the following 4 groups of medicinal plants and substitute varieties thereof, including medicinal parts and non-medicinal parts, medicinal materials and decoction pieces thereof.
Group 1: umbelliferae plants such as bupleuri radix, bupleuri radix processed with vinegar, etc.
Group 2: curcuma aromatica Salisb, Curcuma wenyujin Y.H.Chen et C.Ling, Curcuma longa L.Chen et C.Ling, Curcuma aromatica Salisb, Curcuma longa L.Ling, and Curcuma longa L.Ling.
Group 3: eupatorium, herba Eupatorii, herba Hydrocotyles, herba Eupatorii, etc. belonging to the same family or genus of Eupatorium of Compositae.
Group 4: polygonaceae plants such as Polygoni Multiflori radix and caulis Polygoni Multiflori, and their processed products.
Group 5: cinnamon, cassia twig, cinnamon bark core, cinnamon fragment, cinnamon bark from high mountain, cinnamon bark from low mountain and processed products thereof.
The traditional Chinese medicine substance combination can be obtained by combining the raw materials, extracting with ethanol, other alcohols, diluted alcohol, other organic solvents or water, and purifying by macroporous adsorption resin or other chromatographic methods, such as polyamide chromatography, or solvent extraction.
The traditional Chinese medicine substance combination can be prepared by further enriching and purifying the extracts of the raw material medicines or mixing the macroporous resin preparations of the raw material medicines.
The traditional Chinese medicine substance combination can be obtained by chemical synthesis or structural modification, biosynthesis or biotransformation and other ways.
The traditional Chinese medicine composition is preferably prepared from the following raw material medicines:
100-300 parts of radix bupleuri, 100-300 parts of radix curcumae
100-300 parts of eupatorium fortune and 100-500 parts of prepared fleece flower root
1-200 parts of cinnamon
The preparation method of the drug substance comprises the following steps:
step 1: selecting the raw material medicines;
step 2: steam distillation;
and step 3: extracting with ethanol;
and 4, step 4: purifying with macroporous adsorption resin;
in the step 2, the raw materials (except the radix polygoni multiflori preparata) are distilled by water vapor and extracted by 5-10 times of solvent for 1-10 hours.
In the step 3, the raw materials in the step 2 and the prepared fleece-flower root are extracted by 10 to 80 percent ethanol under reflux for 1 to 3 times, and each extraction is carried out for 0.5 to 2.5 hours; the obtained extract is dissolved in water to obtain an aqueous solution with a concentration of 0.01-0.1 g/mL.
In the step 4, the effective components of the phenols and the terpenes are obtained by passing through a weak-polarity or polar macroporous adsorption resin with the adsorption flow rate of 1-5BV/h, the column diameter-height ratio of the resin of 1: 4-10 and the concentration of the sample loading solution of 0.02-0.1g/mL, eluting with water by 1-5 times the volume of the resin and removing impurities with the water removal flow rate of 1-5BV/h and 10-60% ethanol by 3-10 times the volume of the resin and the elution flow rate of 1-5BV/h, collecting ethanol eluate, recovering the solvent and drying under reduced pressure.
The content of terpenes in the Chinese medicinal extract is 0.5-1.5%, wherein the content of saikosaponin b2 is 0.01-0.6%, the content of phenols is 5-20%, and the preferable content of total phenols is 10-20%.
Adding conventional adjuvants into the extract, and making into pharmaceutically acceptable conventional dosage forms such as capsule, tablet, granule, gel, sustained release preparation, oral liquid, and dripping pill.
The traditional Chinese medicine extract is obtained by subjecting a bupleurum prescription to steam distillation, ethanol extraction and macroporous adsorption resin purification, and is enriched in phenolic components and terpenoid components in the bupleurum prescription, and a mouse replica depression model test proves that the traditional Chinese medicine extract can improve depression behaviors of a model mouse, shorten immobility time of the mouse and inhibit body temperature reduction caused by reserpine.
The principles and features of this invention are described below in conjunction with examples which are set forth to illustrate, but are not to be construed to limit the scope of the invention.
Experimental example 1 Effect of the antidepressant active site of the present invention on the improvement of reserpine antagonistic depressive model mice
(I) test materials
1. Laboratory animal
1.1 Experimental animals
Healthy ICR mice (female, male) weighing 18-20g were provided by Schbefu (Beijing) laboratory animal science, Inc. License number: SCXK (Jing) 2012-0001.
2. Drugs and reagents
The test drugs are: the anti-depression active site of the Chaikaijin prescription is prepared according to the method of example 6, and is dissolved with water to prepare a solution before administration.
The mice dose of fluoxetine hydrochloride (American Gift, Lot 0745A) was 3.33/kg.
(II) Experimental methods and results
1. Grouping and administration of drugs
Rats were randomly divided into 4 groups by weight, namely a blank group, a model group, a positive control group (fluoxetine hydrochloride), a preparation group, an alcohol extract group and a water extract group, 10 rats in each group were continuously administered for 7 days, and the model group and the normal group were administered with equal volumes of water.
2. Experimental methods
Forced swimming experiment of mice: after the sixth administration for 60min, the forced swimming test of the mice is carried out, and the mice are put into beakers with the height of 20cm and the inner diameter of 15cm, wherein one mouse is placed in each jar, the water depth of the jar is 15cm, and the water temperature is 25 +/-1 ℃. After the mice swim for 2min, observation is started immediately, the observation lasts for 4min, and the immobility time (total 6min) of 4min is measured, (the mice stop struggling in water, or the animals are in a floating state and only have small limb movement).
Mouse tail suspension experiment: after the sixth administration for 60min, the mouse tail suspension experiment was performed. The tail of the mouse is fixed with adhesive tape about 1cm away from the tail end, and the mouse is hung upside down with the head about 10cm away from the desktop. After the mouse is hung for 2min, the observation is started immediately, the observation lasts for 4min, the record is not recorded when the mouse moves, a stopwatch is started when the mouse does not move, and the immobility time (the struggle of the mouse in the air or the movement of only tiny limbs) of the mouse 4min after 6min is accumulated.
Reserpine antagonism experiment: before the last administration, reserpine is injected at 4mg/kg except for a blank control group. Standing the mouse after 1h, observing the condition of eyelid ptosis of the experimental animal within 2min, and scoring according to the condition of eyelid ptosis, wherein the scoring standard is as follows: 1/4 of eye closure is 1 minute, 2/4 of eye closure is 2 minutes, 3/4 of eye closure is 3 minutes, and the total closure is 4 minutes; the anal temperature of the mice was measured after 2 h.
3. Statistical analysis: the analysis was performed using the sps 17.0 software, and the experimental results are expressed as mean ± sd. The difference between the groups was determined by comparing each group of mice administered with the model group and the normal group. Statistical method for judging significant difference when alpha is less than 0.05
4. Results of the experiment
TABLE 1 Effect of groups of drugs on mouse behaviourology
Dead time (swimming, tail hanging): p < 0.05 and P < 0.01 are indicated by X, respectively, as compared with the normal group
Scoring of prolapse condition and anal temperature: p < 0.05 and P < 0.01 are plotted against the model group
(III) conclusion
Compared with the model group, the Chaikaifang antidepressive preparation, the alcohol extract and the water extract can improve the depressive behavior of the model mouse, shorten the standing time of the model mouse and inhibit the body temperature reduction caused by reserpine. Compared with the traditional Chinese medicine, the preparation has the advantages of minimum dosage and best drug effect.
The following examples can achieve the effects of the above experimental examples. The particular embodiments are merely illustrative of the invention,
and are not intended to limit the scope of the present invention.
Detailed Description
Example 1: capsule preparation
Bupleurum root, radix Curcumae 100g
Herba Eupatorii 100g radix Polygoni Multiflori Preparata 150g
Cinnamon 15g
Taking 1kg of crude drug decoction pieces according to the proportion, distilling the decoction pieces except the radix polygoni multiflori preparata by using steam, and extracting 9 times of water for 5 hours. Mixing the medicinal materials, and extracting with 70% ethanol under reflux for 1.5 hr for 2 times; dispersing the obtained extract in water to make the water solution concentration 0.01-0.1g/mL, preferably 0.02-0.025 g/mL; (the concentration of phenols is 0.7546mg/ml and the concentration of terpenes is 0.2012mg/ml based on the total crude drug weight).
Adsorbing with DM-130 type macroporous adsorbent resin at an adsorption flow rate of 2BV/h, wherein the ratio of column diameter to height of the resin is 1: 6, the concentration of a sample loading solution is 0.02-0.025g/mL, eluting with water at a flow rate of 1 time of the volume of the resin to remove impurities at a flow rate of 2BV/h, eluting with 30-40% ethanol and 60-70% ethanol at a flow rate of 4-5BV of the resin at an elution flow rate of 2BV/h, collecting the ethanol eluate, recovering the solvent, and drying under reduced pressure to obtain the product. Adding conventional adjuvants, and making into capsule according to conventional process;
the method for measuring the content of terpenes comprises the following steps:
comparison products: saikosaponin b 2;
the determination method comprises the following steps: a chromatographic column: waters Xbridge Shield RP18 (4.6X 250mm, 5 μm); the mobile phase is acetonitrile (A) -0.1 percent (B) formic acid water solution; gradient elution conditions are shown in table 3-2-1, and the column temperature is 30 ℃; the detection wavelength is 190-800 nm; the flow rate is 1.0 mL/min;
TABLE 2 mobile phase gradient elution conditions
The content of terpenoid in the bupleuri radix preparation is 1.4%, and the content of saikosaponin b2 is 0.6%;
the method for measuring the content of phenols comprises the following steps:
comparison products: stilbene glucoside;
reagent: 0.6% ferric trichloride solution, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
the color development method comprises the following steps: precisely sucking a proper amount of sample solution into a 25ml brown volumetric flask, adding 70% methanol to 5ml, then adding 1.6ml of 0.3% sodium dodecyl sulfate solution and 2.4ml of a mixed solution of 0.6% ferric trichloride and 0.9% potassium ferricyanide in a ratio of 1: 1, placing in the dark for 7min, adding 0.1mol/L hydrochloric acid to 25ml of scale mark, shaking up, and placing in the dark for 30min for determination;
the determination method comprises the following steps: and (3) determining the developed sample in a wavelength range of 766 +/-2 nm, recording the maximum absorbance value, and determining that the content of phenols reaches 12%.
Example 2: tablet formulation
Bupleurum root, and Bupleurum root, and
100g of eupatorium fortunei and 100g of prepared fleece flower root
Cinnamon bark 10g
Taking 1kg of crude drug decoction pieces according to the proportion, distilling the decoction pieces except the radix polygoni multiflori preparata by using steam, and extracting 7 times of water for 4 hours. Mixing the medicinal materials, and extracting with 70% ethanol under reflux for 1.5 hr for 3 times; dispersing the obtained extract in water to make the water solution concentration 0.01-0.1g/mL, preferably 0.02-0.025 g/mL; (the concentration of phenols is 0.7546mg/ml and the concentration of terpenes is 0.2012mg/ml based on the total crude drug weight).
Adsorbing with DM-130 type macroporous adsorbent resin at an adsorption flow rate of 2BV/h, wherein the ratio of column diameter to height of the resin is 1: 6, the concentration of a sample loading solution is 0.02-0.025g/mL, eluting with water at a flow rate of 1 time of the volume of the resin to remove impurities at a flow rate of 2BV/h, eluting with 30-40% ethanol and 60-70% ethanol at a flow rate of 3BV/h to remove impurities at a flow rate of 4-5BV of the resin, collecting the ethanol eluate, recovering the solvent, and drying under reduced pressure to obtain the product. Adding conventional adjuvants, and making into tablet according to conventional process;
the method for measuring the content of terpenes comprises the following steps:
comparison products: saikosaponin b 2;
the determination method comprises the following steps: a chromatographic column: waters Xbridge Shield RP18 (4.6X 250mm, 5 μm); the mobile phase is acetonitrile (A) -0.1 percent (B) formic acid water solution; gradient elution conditions are shown in table 3-2-1, and the column temperature is 30 ℃; the detection wavelength is 190-800 nm; the flow rate is 1.0 mL/min;
TABLE 2 mobile phase gradient elution conditions
The content of terpenoid in the bupleuri radix preparation is 1.4%, and the content of saikosaponin b2 is 0.6%;
the method for measuring the content of phenols comprises the following steps:
comparison products: stilbene glucoside;
reagent: 0.6% ferric trichloride solution, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
the color development method comprises the following steps: precisely sucking a proper amount of sample solution into a 25ml brown volumetric flask, adding 70% methanol to 5ml, then adding 1.6ml of 0.3% sodium dodecyl sulfate solution and 2.4ml of a mixed solution of 0.6% ferric trichloride and 0.9% potassium ferricyanide in a ratio of 1: 1, placing in the dark for 7min, adding 0.1mol/L hydrochloric acid to 25ml of scale mark, shaking up, and placing in the dark for 30min for determination;
the determination method comprises the following steps: and (3) determining the developed sample in a wavelength range of 766 +/-2 nm, recording the maximum absorbance value, and determining that the content of phenols reaches 12%.
Example 3: pill preparation
Bupleuri radix 80g, Curcmae rhizoma 80g
Herba Eupatorii 100g radix Polygoni Multiflori Preparata 150g
Cinnamon 15g
Taking 1kg of crude drug decoction pieces according to the proportion, distilling the decoction pieces except the radix polygoni multiflori preparata by using steam, and extracting 5 times of water for 3 hours. Mixing the above materials, extracting with 50% ethanol under reflux for 2 times, each for 2 hr; dispersing the obtained extract in water to make the water solution concentration 0.01-0.1g/mL, preferably 0.02-0.025 g/mL; (the concentration of phenols is 0.7546mg/ml and the concentration of terpenes is 0.2012mg/ml based on the total crude drug weight).
Passing through DM-130 type macroporous adsorption resin with adsorption flow rate of 3BV/h, column diameter-height ratio of 1: 8, sample solution concentration of 0.02-0.025g/mL, eluting with water at 1 time of resin volume to remove impurities with flow rate of 2BV/h, eluting with 30-40% ethanol and 60-70% ethanol at 4-5BV resin volume with elution flow rate of 2BV/h, collecting ethanol eluate, recovering solvent, and drying under reduced pressure. Adding conventional adjuvants, and making into pill according to conventional process;
the method for measuring the content of terpenes comprises the following steps:
comparison products: saikosaponin b 2;
the determination method comprises the following steps: a chromatographic column: waters Xbridge Shield RP18 (4.6X 250mm, 5 μm); the mobile phase is acetonitrile (A) -0.1 percent (B) formic acid water solution; gradient elution conditions are shown in table 3-2-1, and the column temperature is 30 ℃; the detection wavelength is 190-800 nm; the flow rate is 1.0 mL/min;
TABLE 2 mobile phase gradient elution conditions
The content of terpenoid in the bupleuri radix preparation is 1.4%, and the content of saikosaponin b2 is 0.6%;
the method for measuring the content of phenols comprises the following steps:
comparison products: stilbene glucoside;
reagent: 0.6% ferric trichloride solution, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
the color development method comprises the following steps: precisely sucking a proper amount of sample solution into a 25ml brown volumetric flask, adding 70% methanol to 5ml, then adding 1.6ml of 0.3% sodium dodecyl sulfate solution and 2.4ml of a mixed solution of 0.6% ferric trichloride and 0.9% potassium ferricyanide in a ratio of 1: 1, placing in the dark for 7min, adding 0.1mol/L hydrochloric acid to 25ml of scale mark, shaking up, and placing in the dark for 30min for determination;
the determination method comprises the following steps: and (3) determining the developed sample in a wavelength range of 766 +/-2 nm, recording the maximum absorbance value, and determining that the content of phenols reaches 12%.
Example 4: oral liquid preparation
Bupleurum root, radix Curcumae 100g
Herba Eupatorii 80g radix Polygoni Multiflori Preparata 120g
Cinnamon bark 10g
Taking 1kg of crude drug decoction pieces according to the proportion, distilling the decoction pieces except the radix polygoni multiflori preparata by using steam, and extracting the decoction pieces with 6 times of water for 4 hours. Mixing the above materials, extracting with 70% ethanol under reflux for 1 hr for 3 times; dispersing the obtained extract in water to make the water solution concentration 0.01-0.1g/mL, preferably 0.02-0.025 g/mL; (the concentration of phenols is 0.7546mg/ml and the concentration of terpenes is 0.2012mg/ml based on the total crude drug weight).
Passing through DM-130 type macroporous adsorption resin with adsorption flow rate of 3BV/h, column diameter-height ratio of 1: 6, sample solution concentration of 0.02-0.025g/mL, eluting with water at 1 time of resin volume to remove impurities with flow rate of 3BV/h, eluting with 30-40% ethanol and 60-70% ethanol at 4-5BV resin volume with elution flow rate of 2BV/h, collecting ethanol eluate, recovering solvent, and drying under reduced pressure. Adding conventional adjuvants, and making into oral liquid preparation according to conventional process;
the method for measuring the content of terpenes comprises the following steps:
comparison products: saikosaponin b 2;
the determination method comprises the following steps: a chromatographic column: waters Xbridge Shield RP18 (4.6X 250mm, 5 μm); the mobile phase is acetonitrile (A) -0.1 percent (B) formic acid water solution; gradient elution conditions are shown in table 3-2-1, and the column temperature is 30 ℃; the detection wavelength is 190-800 nm; the flow rate is 1.0 mL/min;
TABLE 2 mobile phase gradient elution conditions
The content of terpenoid in the bupleuri radix preparation is 1.4%, and the content of saikosaponin b2 is 0.6%;
the method for measuring the content of phenols comprises the following steps:
comparison products: stilbene glucoside;
reagent: 0.6% ferric trichloride solution, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
the color development method comprises the following steps: precisely sucking a proper amount of sample solution into a 25ml brown volumetric flask, adding 70% methanol to 5ml, then adding 1.6ml of 0.3% sodium dodecyl sulfate solution and 2.4ml of a mixed solution of 0.6% ferric trichloride and 0.9% potassium ferricyanide in a ratio of 1: 1, placing in the dark for 7min, adding 0.1mol/L hydrochloric acid to 25ml of scale mark, shaking up, and placing in the dark for 30min for determination;
the determination method comprises the following steps: and (3) determining the developed sample in a wavelength range of 766 +/-2 nm, recording the maximum absorbance value, and determining that the content of phenols reaches 12%.
Example 5: injection preparation
Bupleurum root, radix Curcumae 100g
100g of eupatorium fortunei and 100g of prepared fleece flower root
Cinnamon 15g
Taking 1kg of crude drug decoction pieces according to the proportion, distilling the decoction pieces except the radix polygoni multiflori preparata by using steam, and extracting 7 times of water for 6 hours. Mixing the medicinal materials, and extracting with 40% ethanol under reflux for 1 time, each for 1.5 hr; dispersing the obtained extract in water to make the water solution concentration 0.01-0.1g/mL, preferably 0.02-0.025 g/mL; (the concentration of phenols is 0.7546mg/ml and the concentration of terpenes is 0.2012mg/ml based on the total crude drug weight).
Passing through DM-130 type macroporous adsorption resin with adsorption flow rate of 1BV/h, column diameter-height ratio of 1: 8, sample solution concentration of 0.02-0.025g/mL, eluting with water at 2 times of resin volume to remove impurities with flow rate of 1BV/h, eluting with 30-40% ethanol and 60-70% ethanol at 4-5BV resin volume with elution flow rate of 3BV/h, collecting ethanol eluate, recovering solvent, and drying under reduced pressure. Adding conventional adjuvants, and making into injection according to conventional process;
the method for measuring the content of terpenes comprises the following steps:
comparison products: saikosaponin b 2;
the determination method comprises the following steps: a chromatographic column: waters Xbridge Shield RP18 (4.6X 250mm, 5 μm); the mobile phase is acetonitrile (A) -0.1 percent (B) formic acid water solution; gradient elution conditions are shown in table 3-2-1, and the column temperature is 30 ℃; the detection wavelength is 190-800 nm; the flow rate is 1.0 mL/min;
TABLE 2 mobile phase gradient elution conditions
The content of terpenoid in the bupleuri radix preparation is 1.4%, and the content of saikosaponin b2 is 0.6%;
the method for measuring the content of phenols comprises the following steps:
comparison products: stilbene glucoside;
reagent: 0.6% ferric trichloride solution, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
the color development method comprises the following steps: precisely sucking a proper amount of sample solution into a 25ml brown volumetric flask, adding 70% methanol to 5ml, then adding 1.6ml of 0.3% sodium dodecyl sulfate solution and 2.4ml of a mixed solution of 0.6% ferric trichloride and 0.9% potassium ferricyanide in a ratio of 1: 1, placing in the dark for 7min, adding 0.1mol/L hydrochloric acid to 25ml of scale mark, shaking up, and placing in the dark for 30min for determination;
the determination method comprises the following steps: and (3) determining the developed sample in a wavelength range of 766 +/-2 nm, recording the maximum absorbance value, and determining that the content of phenols reaches 12%.
Example 6:
bupleurum root, radix Curcumae 100g
Herba Eupatorii 100g radix Polygoni Multiflori Preparata 150g
Cinnamon 15g
Taking 1kg of crude drug decoction pieces according to the proportion, distilling the decoction pieces except the radix polygoni multiflori preparata by using steam, and extracting 7 times of water for 4 hours. Mixing the medicinal materials, and extracting with 70% ethanol under reflux for 1.5 hr for 2 times; dispersing the obtained extract in water to make the water solution concentration 0.01-0.1g/mL, preferably 0.02-0.025 g/mL; (the concentration of phenols is 0.7546mg/ml and the concentration of terpenes is 0.2012mg/ml based on the total crude drug weight).
Through DM-130 type macroporous adsorption resin, the adsorption flow rate is 3BV/h, the height ratio of the resin column diameter is 1: 6, the concentration of a sample loading solution is 0.02-0.025g/mL, the impurities are removed by eluting 2 times of the resin volume with water, the impurity removal flow rate is 2BV/h, the resin volume is 4-5BV by eluting 30-40% ethanol and 60-70% ethanol, the elution flow rate is 3BV/h, the ethanol eluent is collected, the solvent is recovered, and the solvent is dried under reduced pressure, so that the traditional Chinese medicine extract is obtained;
the method for measuring the content of terpenes comprises the following steps:
comparison products: saikosaponin b 2;
the determination method comprises the following steps: a chromatographic column: waters Xbridge Shield RP18 (4.6X 250mm, 5 μm); the mobile phase is acetonitrile (A) -0.1 percent (B) formic acid water solution; gradient elution conditions are shown in table 3-2-1, and the column temperature is 30 ℃; the detection wavelength is 190-800 nm; the flow rate is 1.0 mL/min;
TABLE 2 mobile phase gradient elution conditions
The content of terpenoid in the bupleuri radix preparation is 1.4%, and the content of saikosaponin b2 is 0.6%;
the method for measuring the content of phenols comprises the following steps:
comparison products: stilbene glucoside;
reagent: 0.6% ferric trichloride solution, 0.9% potassium ferricyanide solution, 0.3% sodium dodecyl sulfate solution, 70% methanol solution, 0.1mol/L hydrochloric acid solution;
the color development method comprises the following steps: precisely sucking a proper amount of sample solution into a 25ml brown volumetric flask, adding 70% methanol to 5ml, then adding 1.6ml of 0.3% sodium dodecyl sulfate solution and 2.4ml of a mixed solution of 0.6% ferric trichloride and 0.9% potassium ferricyanide in a ratio of 1: 1, placing in the dark for 7min, adding 0.1mol/L hydrochloric acid to 25ml of scale mark, shaking up, and placing in the dark for 30min for determination;
the determination method comprises the following steps: and (3) determining the developed sample in a wavelength range of 766 +/-2 nm, recording the maximum absorbance value, and determining that the content of phenols reaches 12%.
Example 7: preparation of capsules
Taking 200g of the traditional Chinese medicine composition, crushing, sieving by a 80-mesh sieve, uniformly mixing with 100g of microcrystalline cellulose, granulating by 95% ethanol, drying, grading by a 20-mesh sieve, and filling into capsules.
Example 8: preparation of tablets
Taking 50g of the traditional Chinese medicine composition, crushing, sieving by a 80-mesh sieve, uniformly mixing with 70g of microcrystalline cellulose and 5g of sodium carboxymethyl starch, granulating by 5% PVP, drying, granulating by a 20-mesh sieve, adding 2g of magnesium stearate, and tabletting.
Example 9: preparation of dripping pills
The preparation method comprises the steps of combining 60g of the traditional Chinese medicine substances, crushing, sieving with a 80-mesh sieve, uniformly mixing, putting 180g of heated and melted polyethylene glycol 6000, stirring until the mixture is dissolved, transferring the mixture into a liquid storage bottle, sealing and keeping the temperature at 80-90 ℃, adjusting a liquid drop quantitative valve of a pill dropping machine, dropping the mixture into liquid paraffin with the temperature of 10-15 ℃ from top to bottom, draining the formed dropping pills, wiping off the liquid paraffin, and drying.
Example 10: preparation of oral liquid
Taking 70g of the traditional Chinese medicine composition, crushing, sieving with a 80-mesh sieve, uniformly mixing, mixing with 1000g of honey, 200g of cane sugar, 10g of sodium benzoate and 2000ml of distilled water, heating to 85-90 ℃, stirring for dissolving, keeping the temperature for 30min, filtering, adding water into filtrate for diluting to 4000ml, uniformly stirring, filling and sealing, and sterilizing.
Example 11: preparation of injection
Taking 100g of the traditional Chinese medicine composition, adding a proper amount of water for injection to dissolve the composition, adding 0.02% of activated carbon in a configured amount, stirring for 5-10 min, filtering, diluting the filtrate to about 10L, adding sodium chloride to adjust osmotic pressure to be isotonic, adjusting pH to 7.5-8.0, performing ultrafiltration, filling and sealing, and sterilizing at 100 ℃ for 30 min.
Example 12: preparation of powder injection
Taking 100g of the traditional Chinese medicine substance combination, adding a proper amount of water for injection and dilute sodium hydroxide to dissolve, adding 0.02% of activated carbon in a prepared amount, stirring for 5-10 min, filtering, diluting the filtrate to 1L, adjusting the pH to 6.5-7.8, performing ultrafiltration, performing spray drying, and performing sterile packaging on dry powder. Each 100mg of the injection solution is dissolved by adding a proper amount of water for injection before use, diluted by 250-500 ml of sodium chloride infusion solution and slowly instilled into veins.
Claims (3)
1. A traditional Chinese medicine composition with an antidepressant effect is characterized in that the preparation method of the traditional Chinese medicine composition comprises the following steps:
step 1: selecting 100-300 parts by weight of radix bupleuri, 100-300 parts by weight of radix curcumae, 100-300 parts by weight of eupatorium fortunei, 100-500 parts by weight of radix polygoni multiflori preparata and 1-200 parts by weight of cinnamon;
step 2: distilling bupleuri radix, radix Curcumae, herba Eupatorii and cortex Cinnamomi with steam, and extracting with 5-10 times of solvent for 1-10 hr;
and step 3: mixing the raw materials extracted in step 2 with radix Polygoni Multiflori Preparata, extracting under reflux with 10-80% ethanol for 1-3 times, each for 0.5-2.5 hr; adding water to the obtained extract, dispersing and dissolving to make the concentration of the aqueous solution be 0.02-0.1 g/mL;
and 4, step 4: passing through weak-polar or non-polar macroporous adsorbent resin with adsorption flow rate of 1-5BV/h, column diameter-height ratio of 1: 4-10, sample loading solution concentration of 0.02-0.1g/mL, eluting with water at 1-5 times of resin volume to remove impurities, eluting with 10-60% ethanol at 1-5BV/h and 3-10 times of resin volume, eluting at 1-5BV/h, collecting ethanol eluate, recovering solvent, and drying under reduced pressure to obtain effective components of phenols and terpenes; in the traditional Chinese medicine composition, the content of phenols reaches 12%, the content of terpenes reaches 1.4%, and the content of saikosaponin b2 reaches 0.6%.
2. The preparation prepared from the traditional Chinese medicine composition according to claim 1 is characterized in that various pharmaceutic adjuvants known in the art are added, and any conventional preparation formulation acceptable in pharmacy is prepared according to a conventional preparation process.
3. The use of the pharmaceutical composition of claim 1, in the preparation of a medicament for the treatment of depression.
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| 苏郁滴丸中柴胡郁金提取液的大孔树脂分离纯化工艺;潘爱娟等;《中华中医药学刊》;20091031;第27卷(第10期);第2123-2125页，尤其是第2123页左栏第1段、第2124页左栏第2段及第2125页[6 结论] * |
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