CN111714465B - Jiuwei Shuangjie soft capsule and preparation method thereof - Google Patents

Abstract

The invention belongs to the field of traditional Chinese medicine preparations and the modernization of traditional Chinese medicines, and particularly relates to Jiuwei Shuangjie soft capsules and a preparation method thereof. The Jiuwei Shuangjie soft capsule is composed of a capsule shell and the contents in the capsule shell. The content is a suspension prepared by mixing Jiuwei Shuangjie extract powder, dispersion medium, suspending agent and suspending agent; the extract powder is made of Bupleurum, cooked rhubarb, Qinghao, honeysuckle, Scutellaria baicalensis made from wine, major green leaves, dandelion, Chonglou and peeled ginger made of grass fruit; the capsule shell is made of gelatin, glycerin and water, and the suspension is pressed into the capsule shell by a rotary filming method to make soft capsules. capsule. The Jiuweishuangjie soft capsule provided by the invention has high purity of active ingredients, and the preparation method is environmentally friendly, safe, easy to operate and quality control, low in cost, effectively improves the extraction rate of the Jiuweishuangjie preparation, and obtains Jiuweishuangjie. The soft capsule has stable performance, covers the unpleasant taste of the drug, is easy to swallow, and is suitable for large-scale industrial production.

Description

Jiuwei Shuangjie soft capsule and preparation method thereof

technical field

The invention belongs to the field of traditional Chinese medicine preparations and the modernization of traditional Chinese medicines, and relates to a traditional Chinese medicine preparation and a preparation method thereof, in particular to Jiuwei Shuangjie soft capsules and a preparation method thereof.

Background technique

Jiuwei Shuangjie Oral Liquid is a variety promulgated by the national drug standard (the new drug trial standard is converted into the official standard). It is based on Zhongjingre's good recipe "Da Chai Hu Tang" and the folk secret recipe "Anonymous Gao Shao Tang" based on the theory of traditional Chinese medicine, dialectically treating both symptoms and symptoms and improving it. The whole recipe consists of 9 herbs (rhubarb, honeysuckle, skullcap, dandelion). , Bupleurum, Artemisia annua, Daqingye, Chonglou, Caoguo) among which Bupleurum detoxifies the exterior and relieves fever, rhubarb clears heat and purifies fire, and disperses the exterior and interior of evil things; Artemisia annua removes fire; Honeysuckle detoxifies; Take Daqingye, dandelion, and Chonglou to clear heat and soothe the throat; dry dampness in the temperature of the grass and fruit to make the cold of various medicines. The combination of the nine substances plays both the exterior and interior solutions, which has the functions of relieving exterior heat and clearing away heat, purging fire and detoxifying. Headache, stuffy nose, cough, runny nose, sore throat, thirst, dry stool, etc.

Chinese patent CN201510213827.5 discloses a commercially available Jiuwei Shuangjie oral liquid. The extraction method is as follows: Bupleurum, Artemisia annua, Honeysuckle and Caoguo extract the volatile oil by steam distillation, and the remaining rhubarb, Scutellaria and Daqingye are extracted by steam distillation. , Dandelion, Chonglou five flavors plus 10 times the water soaked and then boiled three times to extract the active ingredients. Under this method, the leaching rate of active ingredients is low and there are many impurities, which is not conducive to refining and affects the efficacy. The dosage form has high requirements for production equipment and process, high cost, special taste and poor patient compliance.

SUMMARY OF THE INVENTION

Without solving the problems existing in the prior art, the object of the present invention is to provide a kind of Jiuwei Shuangjie soft capsule and a preparation method thereof.

The Jiuwei Shuangjie soft capsule provided by the invention has high purity of active components, and the preparation method of the preparation method effectively improves the extraction rate of the Jiuwei Shuangjie preparation, is environmentally friendly, safe, easy to operate and quality control, and has low cost, and the obtained Jiuwei Shuangjie soft capsule Capsules have stable performance, cover up the unpleasant taste of drugs, are easy to swallow, and are suitable for large-scale industrial production.

To achieve the above objects, the present invention provides the following technical solutions.

A Jiuwei Shuangjie soft capsule is composed of a capsule shell and the contents in the capsule shell.

The content is a suspension prepared by mixing Jiuwei Shuangjie extract powder, dispersion medium, suspending agent and suspending agent in a weight ratio of 10:10-15:0.2:0.5.

The extract powder is composed of the following raw materials by weight: 200 parts of Bupleurum, 140 parts of cooked rhubarb, 200 parts of Artemisia annua, 80 parts of honeysuckle, 140 parts of wine-made Scutellaria baicalensis, 155 parts of major green leaves, 140 parts of dandelion , 80 copies of Chonglou, 60 copies of peeled ginger to make grass fruit.

The capsule shell is composed of gelatin, glycerin and water in a weight ratio of 1:0.45:1.

The preparation method of the Jiuwei Shuangjie soft capsule specifically includes the following steps.

Step 1. Preparation of Jiuwei Shuangjie extract powder: extract Bupleurum, honeysuckle, Artemisia annua, Caoguo, Rhubarb, Scutellaria, Daqingye, Dandelion, Chonglou through supercritical CO ₂ extraction combined with steam distillation, It is obtained by extracting, concentrating and drying by the ultrasonic-assisted-reflux extraction method and the ultrasonic-microwave-assisted reflux method, and the specific preparation method is as follows.

(1) Take Bupleurum, Artemisia annua, Honeysuckle and Caoguo and dry them in an oven at 40°C to constant weight, pulverize and sieve (20 mesh).

(2) put the powder described in (1) into the supercritical extraction device, set _CO flow rate to be 2.5Lg/min, extraction kettle pressure 35MPa, separation kettle I pressure 20MPa, 40 ℃, separation kettle II pressure 12MPa, 25 ° C, extract until the volume of volatile oil no longer increases, collect the extract from the mouth of the separation kettle for subsequent use; add water to dissolve the residue, the ratio of material to liquid is 1:50 (g:ml), and extract by steam distillation (temperature does not exceed 80 ° C) Until the volume of volatile oil no longer increases, combine and set aside.

(3) Take rhubarb, Scutellaria, and Chonglou according to the material-to-liquid ratio of 1:30 (g:ml), add 80% ethanol, ultrasonically (55KHz, 250W) at 60°C for 35min, reflux for extraction for 1.5h, filter and recover ethanol, set aside for later use .

(4) Take Daqingye and dandelion and bake them in a 60°C oven to constant weight. After crushing, sieve (40 mesh), add an appropriate amount of 60% ethanol according to the ratio of material to liquid 1:20 (g:ml), put it in an ultrasonic-microwave synergistic extraction apparatus, heat it to 65 ° C, fix the microwave power 100W, ultrasonic power 200W, reflux After extraction for 1.5h, ethanol was recovered by filtration and used for later use.

(5) The solution described in (3) and the solution described in (4) are combined and mixed, and then concentrated to an extract with a relative density of 1.10-1.30 (75° C.).

(6) get the extract described in (5) and the volatile oil described in (2) and mix, add soluble starch in a certain weight ratio according to the amount of the extract while hot, extract: soluble starch=25:1, spray after stirring Dry and pulverize into 120-mesh powder to obtain Jiuwei Shuangjie extract powder.

Step 2, preparation of soft capsules: take gelatin, glycerin and water according to the proportions, and press the suspension into the capsule shell by the rotary film method to prepare soft capsules. The specific preparation method is as follows.

(1) Mix the above-mentioned Jiuwei Shuangjie extract powder with soybean oil, soybean lecithin and beeswax according to the proportion to make a suspension for subsequent use.

(2) Take gelatin, glycerin and water in a ratio of 1:0.45:1 by weight, boil the glue, remove air bubbles under reduced pressure, press filter into a glue storage tank and keep at 60°C for later use.

(3) Then, the suspension described in (1) is compressed into the capsule shell described in (2) by the rotary film method to make soft capsules, and the shape is set below 18-25 °C, and the soft capsules are wiped off with a fiber-free rag. The outer oil layer is dried below 28°C to obtain Jiuwei Shuangjie soft capsules.

Compared with the prior art, the beneficial effects of the present invention are as follows.

(1) the preparation method of Jiuwei Shuangjie soft capsules provided by the invention uses supercritical _CO extraction combined with steam distillation to retain the volatile oil in Bupleurum, Artemisia annua, honeysuckle, and grass fruit to the greatest extent, shortening the extraction time , reduce energy consumption and pollution.

(2) The preparation method of Jiuwei Shuangjie soft capsule provided by the present invention applies ultrasonic-assisted-reflux extraction to process rhubarb, skullcap, and Chonglou so that the yield is greatly improved, the energy consumption is less, the extraction time is short, and the economic benefit is higher .

(3) The preparation method of Jiuwei Shuangjie soft capsule provided by the present invention applies ultrasonic-microwave-assisted reflux method to treat dandelion and Daqingye, destroys plant cell wall and intercellular substance, accelerates the dissolution rate of active ingredients, improves efficiency, and shortens time , reduce the amount of solvent and reduce costs.

(4) The Jiuwei Shuangjie soft capsule provided by the present invention has high content of active ingredients, good stability, lightness to carry and convenient use. And mask the bad smell of Jiuwei Shuangjie oral liquid, improve patient compliance.

Detailed ways

The technical solutions and technical effects of the present invention are described in detail below with reference to specific embodiments. The following embodiments are only preferred embodiments of the present invention, and do not limit the present invention. For those skilled in the art, the present invention may have various modifications and changes. All within the spirit and principle of the present invention, the Any modification, equivalent replacement, improvement, etc., should be included within the protection scope of the present invention.

A Jiuwei Shuangjie soft capsule is composed of a capsule shell and the contents in the capsule shell.

The content is a suspension prepared by mixing Jiuwei Shuangjie extract powder, dispersion medium, suspending agent and suspending agent in a weight ratio of 10:10-15:0.2:0.5.

The extract powder is composed of the following raw materials by weight: 200 parts of Bupleurum, 140 parts of cooked rhubarb, 200 parts of Artemisia annua, 80 parts of honeysuckle, 140 parts of wine-made Scutellaria baicalensis, 155 parts of major green leaves, 140 parts of dandelion , 80 copies of Chonglou, 60 copies of peeled ginger to make grass fruit.

The capsule shell is made of gelatin, glycerol and water in a weight ratio of 1:0.45:1, and the suspension is injected into the capsule shell by a rotary film pressing method to prepare a soft capsule.

The preparation method of described Jiuwei Shuangjie soft capsule is as follows, see implementation one-embodiment three.

Example one.

The preparation method of the Jiuwei Shuangjie soft capsule specifically includes the following steps.

(1) Take 2.0kg of Bupleurum, 2.0kg of Artemisia annua, 0.8kg of Honeysuckle, and 0.6kg of Caojiao, dried in a 40° C. oven to constant weight, pulverized and sieved (20 meshes).

(2) put the powder described in (1) into the supercritical extraction device, set the _CO flow rate to be 2.5L/min, the extraction kettle pressure 35MPa, the separation kettle I pressure 20MPa, 40 ℃, the separation kettle II pressure 12MPa, 25 ℃, extract until the volume of volatile oil no longer increases, collect the extract from the separation kettle mouth for subsequent use; add water to dissolve the residue, the ratio of material to liquid is 1:50 (g:ml), and the steam distillation method is adopted (the temperature does not exceed 80 ℃) Extract until the volume of volatile oil no longer increases, and combine for later use.

(3) 1.4kg of rhubarb, 1.4kg of skullcap, and 0.8kg of Radix Scutellariae were added with an appropriate amount of 80% ethanol, ultrasonicated (55KHz, 250W) for 35min at 60°C, refluxed for extraction for 1.5h, filtered to recover ethanol, and used for later use.

(4) Take 1.55 kg of Daqingye and 1.4 kg of dandelion and bake them in an oven at 60°C to constant weight. After crushing, sieve (40 mesh), add an appropriate amount of 60% ethanol, put it in an ultrasonic-microwave synergistic extraction apparatus, heat it to 65 ° C, fix the microwave power 100W, ultrasonic power 200W, reflux extraction for 1.5h, filter and recover the ethanol, and set aside.

(5) The solution described in (3) and the solution described in (4) are combined and mixed, and the extract is concentrated to a relative density of 1.18 (75° C.).

(6) get the extract described in (5) and the volatile oil described in (2) and mix, add soluble starch in a certain weight ratio according to the amount of the extract while hot, extract: soluble starch=25:1, spray after stirring Dry, pulverize into 120 mesh extract powder.

(7) By weight ratio, the above-mentioned Jiuwei Shuangjie extract powder, soybean oil, soybean lecithin and beeswax are uniformly mixed at 10:15:1:2 to prepare a suspension for subsequent use.

(8) Take gelatin, glycerol and water in a ratio of 1:0.45:1 by weight, boil the glue, remove air bubbles under reduced pressure, press filter into a glue storage tank and keep at 60°C for later use.

(9) Then the suspension described in (7) is pressed into the capsule shell described in (8) by the rotary film method to make a soft capsule, and the shape is set below 25 ° C, and the oil layer on the outer surface of the soft capsule is wiped off with a fiber-free rag. , and dried below 28°C to obtain 10,000 Jiuwei Shuangjie soft capsules.

Example two.

The preparation method of the Jiuwei Shuangjie soft capsule specifically includes the following steps.

(1) Take 200 g of Bupleurum, 200 g of Artemisia annua, 80 g of honeysuckle, and 60 g of grass fruit, and dry them in an oven at 40°C to constant weight, crush and sieve (20 mesh).

(2) put the powder described in (1) into the supercritical extraction device, set _CO flow rate to 2.5Lg/min, extraction kettle pressure 35MPa, separation kettle I pressure 20MPa, 40 ℃, separation kettle II pressure 12MPa, 25 ℃, extract until the volume of volatile oil no longer increases, collect the extract from the separation kettle mouth for subsequent use; add water to dissolve the residue, the ratio of material to liquid is 1:50 (g:ml), and the steam distillation method is adopted (the temperature does not exceed 80 ℃) Extract until the volume of volatile oil no longer increases, and combine for later use.

(3) Add 140 g of rhubarb, 140 g of skullcap, and 80 g of Chonglou in appropriate amount of 80% ethanol, ultrasonically (55KHz, 250W) at 60°C for 35min, reflux for extraction for 1.5h, filter to recover ethanol, and set aside.

(4) Take 155 g of Daqingye and 140 g of dandelion and bake in a 60°C oven to constant weight. After crushing, sieve (40 mesh), add an appropriate amount of 60% ethanol, put it in an ultrasonic-microwave synergistic extraction apparatus, heat it to 65 ° C, fix the microwave power 100W, ultrasonic power 200W, reflux extraction for 1.5h, filter and recover the ethanol, and set aside.

(5) The solution described in (3) and the solution described in (4) are combined and mixed, and the extract is concentrated to a relative density of 1.18 (75° C.).

(6) get the extract described in (5) and the volatile oil described in (2) and mix, add soluble starch in a certain weight ratio according to the amount of the extract while hot, extract: soluble starch=25:1, spray after stirring Dry, pulverize into 120 mesh extract powder.

(7) According to the weight ratio, the suspension prepared by mixing Jiuwei Shuangjie extract powder, soybean oil, soybean lecithin and beeswax at 10:10:0.2:0.5 is ready for use.

(8) Get gelatin, glycerin and water in a ratio of 1:0.45:1 by weight, boil the glue, press filter it into a glue storage tank and keep it at 60°C for later use.

(9) Then the suspension described in (7) is pressed into the capsule shell described in (8) by the rotary film method to make a soft capsule, and the shape is set below 20 ° C, and the outer oil layer of the soft capsule is wiped off with a fiber-free rag. , and dried below 28°C to obtain 1000 Jiuwei Shuangjie soft capsules.

Example three.

The preparation method of the Jiuwei Shuangjie soft capsule specifically includes the following steps.

(1) Take 330 g of Bupleurum, 330 g of Artemisia annua, 130 g of honeysuckle, and 100 g of grass fruit, and dry them in an oven at 40°C to constant weight, crush and sieve (20 mesh).

(2) put the powder described in (1) into the supercritical extraction device, set the _CO flow rate to be 2.5L/min, the extraction kettle pressure 35MPa, the separation kettle I pressure 20MPa, 40 ℃, the separation kettle II pressure 12MPa, 25 ℃, extract until the volume of volatile oil no longer increases, collect the extract from the separation kettle mouth for subsequent use; add water to dissolve the residue, the ratio of material to liquid is 1:50 (g:ml), and the steam distillation method is adopted (the temperature does not exceed 80 ℃) Extract until the volume of volatile oil no longer increases, and combine for later use.

(3) Add 230 g of rhubarb, 230 g of skullcap, and 130 g of Chonglou to an appropriate amount of 80% ethanol, ultrasonically (55KHz, 250W) at 60°C for 35min, reflux for extraction for 1.5h, filter and recover ethanol for use.

(4) Take 255 g of Daqingye and 230 g of dandelion and bake them in an oven at 60°C to constant weight. After crushing, sieve (40 mesh), add an appropriate amount of 60% ethanol, put it in an ultrasonic-microwave synergistic extraction apparatus, heat it to 65 ° C, fix the microwave power 100W, ultrasonic power 200W, reflux extraction for 1.5h, filter and recover the ethanol, and set aside.

(5) The solution described in (3) and the solution described in (4) are combined and mixed, and the extract is concentrated to a relative density of 1.18 (75° C.).

(6) get the extract described in (5) and the volatile oil described in (2) and mix, add soluble starch with a certain weight ratio according to the amount of the extract while hot, extract: soluble starch=25:1, spray after stirring Dry, pulverize into 120 mesh extract powder.

(7) According to the weight ratio, the suspension prepared by mixing Jiuwei Shuangjie extract powder, soybean oil, soybean lecithin and beeswax at 10:10:0.2:0.5 is ready for use.

(8) Take gelatin, glycerol and water in a ratio of 1:0.45:1 by weight, boil the glue, remove air bubbles under reduced pressure, press filter into a glue storage tank and keep at 60°C for later use.

(9) then the suspension described in (8) is filled to the capsule shell described in (9) by the rotary film method to make soft capsules, and the shape is set at 23 ° C, and the outer oil layer of the soft capsule is wiped off with a fiber-free rag, Dry at below 28°C to obtain Jiuwei Shuangjie soft capsules.

Embodiment 4 Determination of the content of functional components in soft capsules and oral liquids.

1. Efficacy components and indicators.

According to the national drug standard WS3-641(Z-091)-2004(Z), the content of Jiuwei Shuangjie Oral Liquid shall be determined based on the amount of rhubarb per 1ml and emodin (C ₁₅ H ₁₀ O ₅ ), not less than 0.095mg index. Therefore, the same as Jiuwei Shuangjie Oral Liquid, the active ingredient of this product is emodin.

2. Determination of the content of functional components in soft capsules and oral liquids.

(1) The content of emodin in this product and Jiuwei Shuangjie oral liquid was determined by HPLC.

The chromatographic conditions are: chromatographic column: Dikma Diamonsil C ₁₈ (200mm×4.6mm; 5μm); mobile phase: methanol-water-0.1% phosphoric acid solution (80:20:0.02); flow rate: 0.8ml·min ⁻¹ ; column temperature : 30°C; injection volume: 10 μL; detection wavelength: 290 nm.

(2) Standard curve determination and sample processing method.

Precisely weigh an appropriate amount of emodin reference substance, add methanol to make a reference substance solution containing 0.1mg of emodin in 1ml. Precisely pipette 2, 4, 6, 8, 10ml of the solution into a 10ml volumetric flask, dilute to the mark with methanol and shake well, respectively pipette 10μL into a high-performance liquid chromatograph for measurement, with peak area A as the ordinate, emodin The concentration C (μg/mL) is the abscissa, and the equation of the standard curve is: Y=4387062.146X-7162.7139, r=0.99998.

Take about 0.3 g of the content of this product, accurately weigh it, put it in a 100 mL volumetric flask, add 60 mL of methanol to dissolve, ultrasonically treat it for 30 minutes, and then adjust the volume to the mark with methanol. Precisely pipette 5mL of the solution, put it in a 10mL volumetric flask, dilute to the mark with methanol, shake well, pipette 10μL into a high performance liquid chromatograph to measure the peak area, and calculate the emodin content of this variety according to the standard curve.

Precisely measure 10ml of Jiuwei Shuangjie Oral Liquid into a 100mL volumetric flask, dilute it to the mark with methanol, draw 10μL and inject it into a high performance liquid chromatograph to measure the peak area, and calculate the emodin content in Jiuwei Shuangjie Oral Liquid according to the standard curve.

(3) The measurement results are shown in Table 1.

Table 1. Measurement results of the content of emodin in Jiuwei Shuangjie Oral Liquid and Example 1 to Example 3.

The above results show that, compared with Jiuwei Shuangjie Oral Liquid, the content of emodin in the soft capsule prepared by the present invention is significantly improved.

EXAMPLES The preparation method of Wujiuwei Shuangjie Soft Capsules was screened experiment.

1. Experiment on the comparative effect of supercritical extraction combined with steam distillation and steam distillation.

1. Preparation of volatile oil.

Supercritical extraction combined with steam distillation method: extract volatile oil according to the operation steps of (2) in Example 1 to Example 3, and calculate the oil extraction rate.

Steam distillation method: prepare samples according to the operation of (1) in Example 1 to Example 3 respectively, add water to dissolve, and put into the steam distillation device (control temperature not more than 80° C.) at a ratio of 1:50 (g:ml) of material to liquid. When the volatile oil no longer increases, the fractions are collected and the oil extraction rate is calculated.

Oil extraction rate=(M ₁ /M ₂ )×100%, where M ₁ is the mass of volatile oil (g); M ₂ is the mass of the sample (g).

2. The measurement results are shown in Table 2.

Table 2. Comparison of volatile oil extraction rates between supercritical extraction combined with steam distillation and steam distillation.

The above results show that compared with steam distillation, the yield of volatile oil extracted by supercritical extraction combined with steam distillation is increased by 11 times, and the extraction time is shortened from 20h to 5h, which reduces energy consumption.

2. Screening experiment of extraction method.

The extraction effects of ultrasonic-assisted-reflux extraction, microwave-assisted-reflux extraction and decoction on rhubarb, skullcap and Chonglou were compared.

Rhubarb, Scutellaria baicalensis and Chonglou medicinal materials were crushed and processed properly (including decoction, ultrasonic-assisted-reflux extraction and microwave-assisted-reflux extraction), and the transfer rates of emodin, baicalin and Chonglou saponins were used as indicators. , to compare the differences between the extraction methods.

1. Processing method.

Decoction method: take 50.00 g of each of the three powders, add 10 times the volume of ultrapure water to soak for 1 hour, decoct and extract twice, 1 hour each time, filter with gauze, and concentrate the filtrate.

Microwave-assisted-reflux extraction method: Weigh 50.00 g of 40 mesh Scutellaria baicalensis powder, add 80% ethanol according to the material-to-liquid ratio of 1:30 (g:ml), microwave at 650W for 35 min, reflux for 1.5 h, and filter to recover ethanol. , concentrated for use.

Ultrasonic-assisted-reflux extraction method: take 50.00g of each of the three powders, add 80% ethanol according to the ratio of solid to liquid 1:30 (g:ml), and then ultrasonically (55KHz, 250W) at 60°C for 35min, reflux for 1.5h extraction, After the ethanol was recovered by filtration, it was concentrated for later use.

2. Determination of standard curve.

Rhubarb: Accurately weigh 20 mg of emodin standard product, put it in a 1000ml volumetric flask, dissolve in methanol, and make up to the mark. Precisely pipette 1mL, 2mL, 3mL, 4mL, and 5mL into a 10ml volumetric flask, add 0.5% magnesium acetate-methanol solution to the mark, and leave for 20min. Taking 0.5% magnesium acetate-methanol solution as blank, the absorbance of the solution at 510nm was measured. A standard curve was plotted as absorbance versus concentration, Y=0.07431X+0.01538, r=0.99998.

Scutellaria baicalensis: Precisely weigh 20.00 mg of baicalin standard, dilute to a 1000 mL volumetric flask with absolute ethanol, accurately pipette 1 mL, 2 mL, 3 mL, 4 mL, and 5 mL, and dilute to a 50 mL volumetric flask with anhydrous ethanol. Water ethanol was used as a blank reference, and the absorbance of baicalin was measured at 278 nm. Taking the absorbance A as the ordinate and the mass concentration of baicalin standard solution (μg/mL) as the abscissa, draw a standard curve, Y=0.10349X+0.01761, r =0.99997.

Chonglou: Accurately weigh 20.00 mg of Chonglou saponin standard, dilute to a 1000mL volumetric flask with methanol, accurately pipette 1mL, 2mL, 3mL, 4mL, 5mL, dilute to a 50mL volumetric flask with methanol, and measure at 415nm The absorbance is taken as the ordinate with A as the ordinate, and the corresponding standard concentration (μg/mL) of C. chinensis is the abscissa, and the standard curve is drawn, Y=48.72251X+0.10739, r=0.99993.

3. Sample processing method.

Rhubarb: add 20ml of 2.5mol/L sulfuric acid to the treated concentrate to hydrolyze for 2h, cool slightly, add 20ml of chloroform, move it to a separating funnel, take the chloroform layer, and continue to extract the acid water layer with chloroform for 3 times, combine, accurately Aspirate 30ml, wash with distilled water until neutral, place the chloroform layer on a water bath and evaporate the chloroform layer, dissolve the residue with 0.5% magnesium acetate-methanol solution, dilute the volume to a 10ml volumetric flask, shake well, leave it for 20min, and measure it by ultraviolet spectrophotometry The absorbance value at 510nm was used to calculate the emodin content.

Scutellaria baicalensis: use the hydrochloric acid solution with a mass fraction of 10% to adjust the pH of the filtrate to 2.0, let it stand in a water bath at 80 °C, and wash the precipitate with anhydrous ethanol for 2-3 times, and dry to obtain crude baicalin. extract. The absorbance value was measured at the wavelength of 278 nm by UV-Vis spectrophotometer, and the content of baicalin was calculated.

Chonglou: add water-saturated n-butanol to the treated concentrate, measure its absorbance value at a wavelength of 415 nm using an ultraviolet-visible spectrophotometer, and calculate the content of Chonglou saponins.

4. The measurement results are shown in Table 3.

Table 3. The extraction effects of different extraction methods on rhubarb, skullcap, and Chonglou.

The above results show that the extraction effect of ultrasonic method is better than that of decoction method and microwave method.

3. Compare the extraction effect of decocting method and ultrasonic-microwave-assisted reflux method on Daqingye and Dandelion.

After appropriate treatment (including decocting method and ultrasonic-microwave-assisted reflux method), the medicinal materials of Daqingye and dandelion were pulverized, and the transfer rates of indirubin and caffeic acid were used as indicators to compare the differences between the extraction methods.

1. Processing method.

Decoction method: take 50.00g of each of the two powders, add 10 times the volume of ultrapure water to soak for 1h, decoct and extract twice, 1h each time, filter with gauze, and concentrate the filtrate.

Ultrasonic-microwave assisted reflux method: take 50.00 g of each of the two powders, add an appropriate amount of 60% ethanol, put them in an ultrasonic-microwave synergistic extraction apparatus to 65°C, fix the microwave power 100W, the ultrasonic power 200W, extract by reflux for 1.5h, filter After the ethanol is recovered, it is concentrated for later use.

2. Chromatographic conditions.

Daqingye: Chromatographic column: Agilent HC-C18 (4.6×250mm, 5μm), methanol-water (75:25) as mobile phase; column temperature 30°C; flow rate 1.0mL/min; detection wavelength 289nm.

Dandelion: Chromatographic column: Agilent HC-C18 (4.6×250 mm, 5 μm); mobile phase is methanol-0.1% phosphoric acid aqueous solution (25:75); column temperature is 30° C.; flow rate is 1.0 mL/min; detection wavelength is 323 mm.

3. Determination of standard curve.

Daqingye: Precisely weigh 20.00 mg of indirubin standard product, dilute it to a 1000mL volumetric flask with methanol, accurately pipette 1mL, 2mL, 3mL, 4mL, and 5mL, and dilute it to a 50mL volumetric flask with methanol. Compatible to the scale, get 6 reference solutions of different concentrations, inject 20 μL of the reference solution respectively, and measure the peak area with the concentration as the abscissa and the peak area as the ordinate to draw a standard curve, Y=18.86003x+38.75421, r = 0.99993.

Dandelion: Precisely aspirate 20.00mg of caffeic acid standard, dilute to a 1000mL volumetric flask with methanol, accurately extract 1mL, 2mL, 3mL, 4mL, 5mL, dilute to a 50mL volumetric flask with methanol, and dilute to the mark with methanol, 6 reference substance solutions of different concentrations were obtained, 20 μL was injected into the high performance liquid chromatograph, and the peak area was measured with the concentration as the abscissa and the peak area as the ordinate to draw a standard curve, Y=63.67064X-0.25429, r=0.99998.

4. Sample processing method.

Take 0.3 g of the two medicinal material concentrates prepared under different treatment methods, accurately weigh them, put them in a 100 mL volumetric flask, add 60 mL of methanol to dissolve, ultrasonically treat for 30 min, and then adjust the volume to the mark with methanol. Precisely pipette 5mL of the solution, put it in a 10mL volumetric flask, dilute to the mark with methanol, shake well, draw 20μL and inject it into a high performance liquid chromatograph to measure the peak area, and calculate the content of indirubin and caffeic acid according to the two standard curves.

5. The measurement results are shown in Table 4.

Table 4. The extraction effects of different extraction methods on Daqingye and Dandelion.

The above results show that the extraction effect of ultrasonic-microwave-assisted reflux method is better than that of decoction.

The disintegration time limit and stability of embodiment 69 flavor Shuangjie soft capsules were investigated.

1. Disintegration time limit investigation.

Taking Example 1 to Example 3 as the test samples, each took 6 capsules and put them into a lift-type disintegrator for inspection. The artificial gastric juice was filled in the beaker, and the temperature was set to 37°C. After testing, the soft capsules made in Example 1 to Example 3 all meet the standard. The specific experimental results are shown in Table 5.

Table 5. Determination of disintegration time for Example 1 to Example 3 (n=6).

2. Stability inspection.

Take Example 1 to Example 3 as the test samples, take three batches of the test samples respectively, place them for 12 months under the conditions of temperature 25 ℃ ± 2 ℃, relative humidity 60% ± 5%, and regularly investigate preparation properties, disintegration time limit and Changes in emodin content. The results showed that after 12 months, the preparation had no adhesion, no leakage, and no precipitation in the contents. The lowest content drop was 1.40%, and the highest drop was only 2.34%. The stability was good. The results are shown in Table 6.

Table 6. Stability investigation of examples one to three.

To sum up, the Jiuwei Shuangjie soft capsule prepared by the present invention has high extraction rate, good stability and low energy consumption, and is suitable for industrial production.

Claims (1)

1. The preparation method of the Jiuwei Shuangjie soft capsule is characterized by comprising the following steps:

step 1, preparation of Jiuwei Shuangjie extract powder:

(1) drying bupleuri radix, herba Artemisiae Annuae, flos Lonicerae and fructus Tsaoko at 40 deg.C in oven to constant weight, pulverizing, and sieving with 20 mesh sieve;

(2) putting the powder prepared in the step (1) into a supercritical extraction device, and setting CO₂The flow rate is 2.5Lg/min, the pressure of an extraction kettle is 35MPa, the pressure of a separation kettle I is 20MPa and 40 ℃, the pressure of a separation kettle II is 12MPa and 25 ℃, and the extract is collected from the opening of the separation kettle for standby after the volume of the volatile oil is not increased any more; and adding water to dissolve the residue, wherein the material-liquid ratio is 1:50(g: mL), extracting by steam distillation at a temperature not higher than 80 deg.C until the volume of volatile oil is not increased, and mixing;

(3) taking rhubarb, scutellaria and rhizoma paridis according to a material-liquid ratio of 1: adding 80% ethanol into 30(g: mL), performing ultrasonic treatment at 60 deg.C under 55KHz for 35min under 250W, reflux extracting for 1.5h, filtering, and recovering ethanol;

(4) drying folium Isatidis and herba Taraxaci in a 60 deg.C oven to constant weight, pulverizing, sieving with 40 mesh sieve, adding appropriate amount of 60% ethanol according to a material-liquid ratio of 1:20(g: mL), heating to 65 deg.C in an ultrasonic-microwave synergistic extraction apparatus, fixing microwave power of 100W and ultrasonic power of 200W, reflux extracting for 1.5h, filtering, and recovering ethanol;

(5) mixing the solution prepared in the step (3) and the solution prepared in the step (4), uniformly mixing, and concentrating to obtain an extract with the relative density of 1.10-1.30 (75 ℃);

(6) uniformly mixing the extract in the step (5) with the volatile oil in the step (2), and adding soluble starch according to a certain weight ratio of the extract amount when the extract is hot: soluble starch = 25:1, stirring, spray-drying, and crushing into 120-mesh powder to obtain nine-ingredient Shuangjie extract powder;

step 2, preparing the soft capsule:

(1) mixing the above nine-ingredient double-decomposition extract powder with soybean oil, soybean phospholipid and Cera flava uniformly according to a ratio to obtain suspension;

(2) according to the weight ratio of 1:0.45:1, taking gelatin, glycerol and water according to the proportion, boiling the gelatin, removing bubbles under reduced pressure, and performing filter pressing on the gelatin to a gelatin storage tank for keeping the temperature at 60 ℃ for later use;

(3) and (3) filling and pressing the suspension in the step (1) into the capsule shell prepared in the step (2) by a rotary film pressing method to prepare a soft capsule, shaping at the temperature of below 18-25 ℃, wiping off an oil layer on the surface of the soft capsule by using a non-fiber rag, and drying at the temperature of below 28 ℃ to obtain the nine-ingredient double-effect soft capsule.