CN101259179A - Chinese medicine 'naodesheng' soft capsule and preparation thereof - Google Patents

Abstract

The soft naodesheng capsule of a Chinese patent medicine comprises capsule materials and medicine. The mass ratio of medicine composition is as follows: 20 to 35 percent valid target groups, 57 to 72 percent edible vegetable oil, 2 to 6 percent cera flava and 0 to 2.5 percent lecithin. The valid target groups are mixed by crude drugs converted from three valid targets according to extraction rate as follows: 6 to 9 portions of gegen, hawthorn and the extract of safflower flavone, 1 to 1.5 portions of notoginseng saponins and 0.8 to 1.2 portions of hemlock parsley oil. The preparation method is: the gegen, the hawthorn and the safflower are mixed according to the mass ratio and extracted by ethanol; the extracts are dissolved in water and purified by D-101 macroporous resin to obtain the extract of the flavone; and critical CO2 is used for extracting the hemlock parsley to obtain the hemlock parsley oil. The extract of the flavone is mixed with the total notoginseng saponins (available in market) and the vegetable oil, the cera flava and the lecithin are proportionally added and evenly mixed with the hemlock parsley oil to obtain mixing suspension; gelatin, glycerol, sorbitol, citric acid, titanium dioxide and water are proportionally made into glue solution; and finally the suspension and the glue solution are put into a production equipment used for producing the soft capsule to crank out the soft capsule.

Description

Chinese medicine soft capsule Naodesheng and preparation method thereof

Technical field

The invention belongs to a kind of Chinese medicine, specifically be meant a kind of blood circulation promoting and blood stasis dispelling that has, the effect of dredge the meridian passage is used for dizzy, apoplexy due to the obstruction of collaterals by blood stasis, disease see limbs need not, speech is unfavorable and have a dizzy spell; The Chinese patent medicine of cerebral arteriosclerosis, ischemia apoplexy and apoplexy sequela patient---NAODESHENG active site extraction and purification process and preparation of soft capsule method thereof.

Background technology

Cardiovascular and cerebrovascular disease is frequently-occurring non-infectious chronic disease, and its case fatality rate is first of the three big noninfectiouss.Announce according to Chinese cardiovascular and cerebrovascular vessel control net: have an appointment 8% people of the world suffers from cardiovascular and cerebrovascular disease, China is one of country that the cardiovascular and cerebrovascular disease sickness rate is the highest in the world, and being ascendant trend year by year, sum has been much higher than the U.S., Canada, France, Switzerland, Japan and other countries.In recent years, cardiovascular and cerebrovascular disease morbidity and death present rejuvenation trend.The patient that myocardial infarction, cerebral infarction and cerebral hemorrhage took place about 30 years old is more and more.In case morbidity, the lighter is disabled, weight person's death.Bring heavy losses for individual, family and society.So it is very urgent to treat cardiovascular and cerebrovascular disease effectively.

NAODESHENG PIAN is recorded in " one one of Chinese pharmacopoeia version in 2005 is made up of Radix Notoginseng, Rhizoma Chuanxiong, Flos Carthami, Radix Puerariae, Fructus Crataegi Chinese medicine of the five flavours.The little hardship of Radix Notoginseng in the side, warm in nature and battalion's row stagnates, and blood circulation promoting and blood stasis dispelling is thought monarch drug.The sweet suffering of Radix Puerariae, cool in nature, elevate a turnable ladder be sun clearly, the expelling pathogenic factors from muscles collateral dredging; The hot temperature of Flos Carthami is invigorated blood circulation, and stimulates the menstrual flow, and eliminating stasis to stop pain is ministerial drug altogether, to strengthen monarch drug blood circulation promoting and blood stasis dispelling, the merit of the numbness of promoting blood circulation out.Assistant is with the hot temperature of Rhizoma Chuanxiong, blood-activating and qi-promoting, wind-expelling pain-stopping; Crataegolic acid is sweet, tepor, and blood circulation promoting and blood stasis dispelling, the removing food stagnancy blood fat reducing is adjuvant drug altogether.Full side plays blood circulation promoting and blood stasis dispelling, the effect of dredge the meridian passage altogether.Be used for dizzy, apoplexy due to the obstruction of collaterals by blood stasis, disease see limbs need not, speech is unfavorable and have a dizzy spell; Cerebral arteriosclerosis, ischemia apoplexy and apoplexy sequela are seen above-mentioned patient.

Modern study shows: 1. the main active of Radix Notoginseng is a Radix Notoginseng total arasaponins, has blood vessel dilating, reduces myocardial oxygen consumption, suppresses platelet aggregation, prolongs pharmacological actions such as clotting time, blood fat reducing, removing free radical, antiinflammatory, antioxidation, fibrosis; Cerebral hemorrhage injured neurons, cerebral ischemic injury, the infringement of alzheimer disease pathology are had the protective effect of using, and can promote retinal ganglion cell regeneration.2. the volatile oil of Rhizoma Chuanxiong can suppress the formation and the platelet aggregation of thrombosis, and microcirculation improvement reduces vascular resistance, and ischemic diseases is had significant curative effect.3. the main active of Flos Carthami is a flavones ingredient, has blood vessel dilating, brings high blood pressure down, removes oxygen-derived free radicals, effects such as anticoagulant, anti-cerebral ischemia, alleviation thrombosis, protection cranial nerve cell.4. the main active site of Radix Puerariae is a Radix Puerariae total flavones, mainly act as blood pressure lowering, anti-arrhythmia, coronary artery dilating and cerebrovascular, reducing blood sugar and blood fat, antioxidation, anticoagulant etc.5. total flavones has heart tonifying, blood pressure lowering, cholesterol reducing, coronary artery dilating and vasodilator, increase coronary flow, improves effects such as heart vigor in the Fructus Crataegi; The triterpene acids has effects such as blood fat reducing, increase coronary vasodilator blood flow.

The former preparation of NAODESHENG is pill, tablet, and there is following deficiency in its preparation technology: 1. use medical material crude drug powder directly to be used as medicine, easily pollute; 2. former dosage form is sheet (ball) agent, and disintegrate is slow, absorption difference in the body, and bioavailability is low; 3. water extraction process can not fully extract the active component of medicine; 4. traditional processing technology, taking dose is big, and quality controllability is poor.

Summary of the invention

The objective of the invention is to adopt supercritical CO ₂The traditional processing technology of modern general character key technology reform such as extraction, purification by macroporous resin NAODESHENG, with its be developed into that active component is highly enriched, impurity is few, quality controllable, bioavailability is high, can give full play to herbal species---the soft capsule Naodesheng of Drug therapy effect, and a kind of preparation method of described soft capsule Naodesheng is provided simultaneously.

Chinese medicine is Radix Notoginseng, Rhizoma Chuanxiong, Flos Carthami, Radix Puerariae, Fructus Crataegi among the present invention, it is characterized in that each component adopts effective part extract to be used as medicine: Radix Notoginseng total arasaponins, Rhizoma Chuanxiong supercritical CO ₂Extract (Rhizoma Chuanxiong oil), Flos Carthami, Radix Puerariae and Fructus Crataegi total flavones.

Chinese patent medicine soft capsule Naodesheng of the present invention comprises soft capsule material and content, and content is formed and mass percent is:

Effective part group 20～35%

Edible vegetable oil 57～72%

Yellow beeswax 2～6%

Lecithin 0～2.5%;

Described effective part group is that following three effective sites are amounted to into the mixing of crude drug amount by extraction ratio, and its ratio of quality and the number of copies is: 6～9 parts of Radix Puerariae, Fructus Crataegi and Flos Carthami extractive of general flavone, 1～1.5 part of arasaponin: 0.8～1.2 part of Rhizoma Chuanxiong oil;

Described edible vegetable oil comprises soybean oil, Oleum Brassicae campestris, Oleum Helianthi, Oleum Arachidis hypogaeae semen, siritch, the mixture of one or two or more kinds in Oleum sesami, Semen Maydis oil, the Oleum Gossypii semen.

The raw material of described soft capsule material and ratio of quality and the number of copies are: 1 part in gelatin, 0.3～0.6 part of glycerol, 0.05～0.15 part of sorbitol, 0.04～0.08 part of citric acid, 0.005～0.015 part of titanium dioxide, 1.1～1.3 parts in water.

The preparation method of Chinese patent medicine soft capsule Naodesheng of the present invention comprises the steps:

1), by following ratio of quality and the number of copies weighting raw materials: 78 parts of Radix Notoginseng or Radix Notoginseng total arasaponins (commercially available product) 2.73-5.46 part, 91 parts on Flos Carthami, 261 parts of Radix Puerariaes, 157 parts of enucleation Fructus Crataegis;

2), described Radix Puerariae, Fructus Crataegi and Flos Carthami are together got carried total flavones and get and carry thing, the extracting method step is: get Radix Puerariae, the mixing of Fructus Crataegi and Flos Carthami decoction pieces, the alcohol reflux three times that adds concentration 60-80%, for the first time the ethanol extraction of 10 times of amounts of dosing material amount is 2 hours, adds the ethanol extraction 1 hour of 8 times of amounts for the second time, adds the ethanol extraction 1 hour of 6 times of amounts for the third time, merge 3 times extracting solution, decompression recycling ethanol is concentrated to no ethanol flavor, must extract concentrated solution; Add water to every milliliter and contain crude drug 0.1 gram, filter, get filtrate; Filtrate is crossed D 101 macroporous resin column adsorb, wash with water and ethanol elution, absorption, washing and ethanol elution process conditions are: the adsorption liquid flow velocity be 1-3 times of column volume/hour, absorption liquid measure be 4-5 times of column volume; The washing speed be 3 times of column volumes/hour, the washing volume be 4-6 times of column volume; The eluting concentration of ethanol is 30-60%, flow velocity be 1-3 times of column volume/hour, consumption is a 2-6 times of column volume; Collect ethanol elution, being concentrated into density is the 1.05-1.10 grams per milliliter, and spray drying obtains Radix Puerariae, Fructus Crataegi and Flos Carthami 3 flavor Chinese medicines close extract, total flavones mass content 78.1% in the extract;

3), described Rhizoma Chuanxiong is extracted Rhizoma Chuanxiong oil, the extracting method step is: the Rhizoma Chuanxiong pulverizing medicinal materials is crossed 20 mesh sieves, places supercritical CO ₂Extract in the extraction equipment, extraction conditions is: 60 ℃ of extraction temperature, extracting pressure 35Mpa, 2 hours extraction time.Collect extract, the treated Rhizoma Chuanxiong oil that obtains, oil-collecting ratio are 5.4%;

4) with step 2) extractive of general flavone that obtains mixes with Radix Notoginseng total arasaponins (commercially available product), add edible vegetable oil, yellow beeswax, lecithin in proportion, the Rhizoma Chuanxiong oil mixing that obtains with step 3), make suspension, wherein material mass percentage ratio is: effective part group 20～35%: edible vegetable oil 57～72%: yellow beeswax 2～6%: lecithin 0～2.5%;

5) press ratio of quality and the number of copies, 1 part in gelatin, 0.3～0.6 part of glycerol, 0.05～0.15 part of sorbitol, 0.04～0.08 part of citric acid, 0.005～0.015 part of titanium dioxide and water are made glue for 1.1～1.3 parts;

6), the glue that obtains of suspension that step 4) is obtained and step 5) places the soft capsule production equipment to make soft capsule.Every ball 0.35～0.5 gram.

Fructus Crataegi described in the present invention is an enucleation Fructus Crataegi decoction pieces.

The % of concentration of alcohol described in the present invention is meant in the 100 volume ethanol aqueous solutions and contains the ethanol volume fraction.

The present invention compared with prior art has following advantage:

1, adopts modern general character key technology---supercritical CO ₂Extraction, purification by macroporous resin technical point are got Rhizoma Chuanxiong oil and Radix Puerariae, Fructus Crataegi and Flos Carthami total flavones indescribably, can fully extract active component, remove impurity component.

2, with effective site be the crude drug prescription, its development is soft capsule Naodesheng, this dosage form has novelty attractive in appearance, dosage is accurate, dose is little, carry convenient transportation, effective ingredient is clear and definite, quality controllability is strong.

Description of drawings

Fig. 1 technological process of production figure

Fig. 2 Radix Puerariae, Fructus Crataegi and Flos Carthami extracting solution sample solution are crossed the leakage plot of D101 macroporous resin column absorption total flavones

Fig. 3 washes volume and total flavones loss relation curve

Fig. 4 washes volume and dried cream series of fortified passes is a curve

Figure 54 0% ethanol is the elution curve of total flavones in the eluant eluting resin column

Technological process shown in Figure 1 is: 1. get the three flavor prepared slices of Chinese crude drugs (91 parts on 261 parts of the roots of kudzu vine, 157 parts of hawthorn and safflower) 14 Kilogram extracts 3 times with 70% alcohol reflux, and for the first time with 140 liters of ethanol, refluxing extraction 2 hours is used ethanol for the second time Being 112 liters, is 84 liters with ethanol for the third time, and respectively refluxing extraction is 1 hour, and the hawthorn extract that obtains for 3 times merges, and returns Receive ethanol, be concentrated to no ethanol flavor, release to 140 liters, filter for subsequent use; Filtrate is passed through macropore with 1 times of column volume/hour speed Resin (medicinal material: D-101 macroreticular resin=1: 3), rush 5 times of posts in order to 3 times of column volumes/hour speed earlier after the absorption fully Volume distilled water uses 40% ethanol of 5 times of column volumes with identical flow velocity wash-out again, collects eluent, and eluent is concentrated into suitable The amount volume, spray-drying gets the root of kudzu vine, hawthorn and safflower extract. 2. get Ligusticum chuanxiong Hort 2.145kg, be ground into meal (mistake 20 mesh sieves), put supercritical CO₂Extract in the extraction equipment, extraction conditions is: 60 ℃ of extraction temperature, extracting pressure 35Mpa, Extraction time 2h. Collect extract, the treated cnidium oil that obtains. 3. get arasaponin 0.15kg and extractive of general flavone Mix, add in proportion vegetable oil, cera flava, with the cnidium oil mixing, make suspension. 4. with gelatin, glycerine, sorb Alcohol, citric acid, titanium dioxide, water are made glue in proportion. Place the soft capsule production equipment to make suspension and glue Soft capsule.

The specific embodiment

Below in conjunction with embodiment the inventive method is further specified.

The extraction purification of embodiment 1 Radix Puerariae, Fructus Crataegi and Flos Carthami total flavones

1. the extraction process of Radix Puerariae, Fructus Crataegi and Flos Carthami total flavones experiment.

(1) presses mass ratio, get 91 parts on Flos Carthami, 261 parts of Radix Puerariaes, 157 parts of Fructus Crataegis (enucleation); The use ethanol reflux extraction experimentizes, and adopts L ₉(3 ⁴) orthogonal experiment method investigates the technological parameter of factors such as concentration of alcohol, ethanol consumption (multiple of quality of medicinal material), extraction time in alcohol reflux Radix Puerariae, the Fructus Crataegi and Flos Carthami total flavones, and adopt ultraviolet visible spectrophotometry that content of total flavone in the extract is measured, measure the content of puerarin and S-A Hydroxysafflor yellow A simultaneously with high-efficient liquid phase technique, and compare analysis as index.The results are shown in Table 1, table 2, table 3, table 4, table 5.

Table 1 experimental factor water-glass

Table 2 L ₉(3 ⁴) orthogonal design table

The variance analysis of table 3 total flavones amount

The variance analysis of table 4 puerarin amount

The variance analysis of table 5 S-A Hydroxysafflor yellow A amount

Orthogonal experiments shows (see Table 3, table 4), influence factor's maximum be extraction time.Concentration of alcohol, the ethanol consumption does not have obvious influence, and it is A that intuitive analysis goes out optimum extraction process ₂B ₃C ₃

From S-A Hydroxysafflor yellow A variance analysis (table 5), each factor is to the content there was no significant difference of S-A Hydroxysafflor yellow A.It is A that intuitive analysis goes out optimum extraction process ₂B ₃C ₃In sum, selected only process conditions are, 70% ethanol extracts 3 times, and extraction time (multiple) is respectively 2 hours (10 times), 1 hour (8 times), 1 hour (6 times).

(2) demonstration test: get Radix Puerariae, Fructus Crataegi and Flos Carthami decoction pieces (261 parts of Radix Puerariaes, 91 parts of 157 parts of and Flos Carthami of Fructus Crataegi), totally 3 parts, carry out demonstration test according to preferred extraction process, demonstration test result such as table 6:

Table 6 extraction process authentication result of the test

Demonstration test result shows that preferred extraction process stablizes feasible.

2. the purification by macroporous resin technological experiment of Radix Puerariae, Fructus Crataegi and Flos Carthami total flavones

The extracting solution that obtains with aforementioned preferred extraction conditions carries out following experiment:

(1) D-101 resin purification technological experiment

1. adsorption conditions optimization experiment

Adopt orthogonal test method, use sample liquor strength (in the crude drug amount that is contained in the sample), blade diameter length ratio and go up the sample flow velocity, use L as investigating factor ₉(3 ⁴) orthogonal table arrangement test, factor and level arrangement see Table 7.General flavone content is measured in above 9 groups of tests respectively, and estimated.Analysis result sees Table 8, table 9.

Table 7 factor level table

Table 8 orthogonal experiments

Table 9 variance analysis

Intuitive analysis shows, 3 factors are to Radix Puerariae, the influence degree of the adsorption efficiency of Fructus Crataegi and Flos Carthami total flavones on macroporous adsorbent resin is followed successively by: last sample concentration (A)＞last sample flow velocity (D)＞blade diameter length ratio (B), ANOVA showed significant, at Radix Puerariae, in the adsorption process of Fructus Crataegi and Flos Carthami total flavones, the A factor has appreciable impact, take all factors into consideration, preferred compositions is A ₂B ₁D ₃

2. applied sample amount is investigated

Get 0.1 grams per milliliter sample solution, be added on the 20 gram D-101 resin columns (blade diameter length ratio 1: 7), with 1 times of column volume/hour flow velocity pass through.Each flow point is collected 10 milliliters, measures and calculate the concentration of total flavones in the flow point.Measurement result is seen Fig. 2.Beginning is obviously leaked (to be about 3.5 times of column volumes) as can be seen when applied sample amount is 70 milliliters among the figure, and 150 milliliters to reach absorption saturated.Take all factors into consideration and determine that it (is crude drug: resin=1: 3) that last sample volume is 70 milliliters.

3. washing amount is investigated

Get 0.1 grams per milliliter sample solution 70ml, be added on the 20 gram D101 resin columns (blade diameter length ratio 1: 7), with 1 times of column volume/hour flow velocity pass through.The reuse distilled water is with 2 times of column volumes/speed at one hour rating eluting, and each flow point is collected 10 milliliters, measures and calculate total flavones amount (see figure 3) and the heavy (see figure 4) of dried cream in the flow point.As seen from the figure, in the water elution liquid behind 5 times of column volumes flavone loss bigger, so determine that the washing volume is 5 times of column volumes.

4. ethanol elution concentration is investigated

Other gets five parts of upper props of 20g resin, adsorb by above condition, after the flushing of 5 times of cylinder hydrops, respectively with an amount of 30%, 40%, 50%, 60%, 70% ethanol with 2 times of column volumes/hour the flow velocity eluting, measure general flavone content in the eluent, calculate eluting rate; Volatilize solvent, with the extractum weight, the accurate title, decide and calculate content of total flavone, the results are shown in Table 10.

The amount of total flavones in the table 10 variable concentrations eluent

Take all factors into consideration the total flavones purity and the rate of transform and select 40% ethanol elution for use.

5. elution rate is investigated

Carrying out dynamic adsorption by above-mentioned condition, is eluant with 80% ethanol, respectively with 2,3,4 times of column volumes/hour the speed eluting, measure in the ethanol elution thing total flavones amount and calculate eluting rate, the result show elution rate be 3 times of column volumes/hour the time eluting rate the highest.

6. the ethanol elution amount is investigated

Carrying out dynamic adsorption by above-mentioned condition, is that eluant carries out eluting with 40% ethanol, and the quantitative collection effluent is also measured wherein total flavones concentration.The results are shown in Figure 5.

The result shows: with 100 milliliters of (about 5 times of column volumes) 40% ethanol with 2 times of column volumes/hour flow velocity adsorbed flavones ingredient of eluting 20g resin fully.

3. pilot scale amplification test

Take by weighing 14 kilograms of Fructus Crataegi decoction pieces, 70% alcohol reflux 3 times, for the first time with 140 liters of ethanol, reflux, extract, 2 hours, with 112 liters of ethanol, reflux, extract, 1 hour is used 84 liters of ethanol for the third time for the second time, and reflux, extract, is 1 hour respectively.Merge 3 times extracting solution, reclaim ethanol to there not being the alcohol flavor, placement is spent the night, and inferior daily filter cloth filtering precipitation is diluted to every milliliter of solution that contains crude drug 0.1 gram, and is standby.

With 20 kilograms of an amount of soak with ethanol of pharmaceutical grade D101 type macroporous resin, the wet method upper prop, standby after handling.

Extract medicinal liquid and go up sample adding resin column at twice, each 70 liters, last sample flow velocity be 1 times of column volume/hour, earlier with the distilled water flushing of 5 times of column volumes, 5 times of column volume 40% ethanol of reuse are collected ethanol elution with 3 times of column volumes/hour flow velocity eluting behind the last sample, be concentrated into small size (density is about 1.05 grams per milliliters), spray drying (the spray dryer intake air temperature is 170 ℃, and the air outlet temperature is 85 ℃, and the atomizing disk rotating speed is 20000 rev/mins).Collect dry extract, seal, put coldly, weigh, put dry place and preserve.Adopt ultraviolet visible spectrophotometry to measure content of total flavone in the extract, calculate the rate of transform (in the rate of transform=extract in content of total flavone/crude drug content of total flavone * 100%) and receive cream rate (receipts cream rate=extract gross mass/crude drug gross mass * 100%).Result of the test sees Table 11.

Table 11 pilot experiment result

Three batches of pilot scales are amplified result of study and shown: its Fructus Crataegi total flavones rate of transform reaches 84.23%, and general flavone content 79.27% in the extract.The technological parameter that shows this research is feasible, and stable process conditions is expected to carry out the transition to industrialization production.

Embodiment 2 supercritical carbon dioxide extraction methods extract the process of Rhizoma Chuanxiong oil

The design of employing orthogonal experiment, slective extraction pressure, temperature, time 3 factors, each factor designs 3 levels (seeing Table 12) respectively.The pressure of setting separating still is 5～6MPa, 45 ℃ of temperature, CO ₂Flow is about 20 liters/hour; Take by weighing Rhizoma Chuanxiong medicinal material coarse powder (crossing 20 mesh sieves) 300 grams (totally 9 parts), with L ₉(3 ⁴) orthogonal table arrangement test (the results are shown in Table 13), extract respectively.Collect extract, the reuse extracted with diethyl ether, ether layer is flung to solvent after with anhydrous sodium sulfate dehydration, clear and bright rufous Rhizoma Chuanxiong oil.Oil-collecting ratio is an important indicator of weighing effect of extracting, and ferulic acid is one of effective ingredient of Rhizoma Chuanxiong oil, therefore with the two all as evaluation index, comprehensive grading (oil-collecting ratio scoring coefficient 0.7, ferulaic acid content scoring coefficient 0.3), interpretation of result sees Table 12-13.

Table 12 orthogonal test factor level table

Table 13 orthogonal experiments

Annotate: oil-collecting ratio scoring=(70/ maximum oil-collecting ratio) * oil-collecting ratio; Ferulaic acid content scoring=(30/ maximum ferulaic acid content)

* ferulaic acid content; Comprehensive grading=oil-collecting ratio scoring+ferulaic acid content scoring

Table 14 The results of analysis of variance

Annotate: F _{(0.05 2,2)}=19 F _{(0.01 2,2)}=99

Variance analysis (table 14) shows that factor A and B are extremely remarkable to the result of the test influence, and factor D influence significantly.Optimum process condition is A ₃B ₃C ₃D ₂, promptly extraction temperature is 60 ℃, extracting pressure 35Mpa, extraction time 2h.For further investigating the reliability and the stability of selection process, to get 3 parts of medical materials and carry out demonstration test by above-mentioned optimum extraction process condition, operational approach is the same, and measurement result sees Table 15.

Table 15 demonstration test result

Three times the demonstration test result shows, average oil-collecting ratio is 5.52%, and ferulaic acid content is 254.6mg, with orthogonal test preferred result basically identical, shows that this selection process stablizes feasible.

On the basis of process certification, carry out middle trial production.Take by weighing Rhizoma Chuanxiong pharmaceutical decocting piece 10kg, pulverize, cross 20 mesh sieves, the powder of getting it filled places supercritical CO ₂In the extraction equipment, extract, collect extract by above-mentioned optimizing technology parameters, the treated 538.5g Rhizoma Chuanxiong oil that obtains, oil-collecting ratio is 5.4%, the results are shown in Table 16.

Table 16 pilot scale extraction process condition

The moulding process of embodiment 3 compound Naodesheng soft capsules

The compound Naodesheng soft capsule preparation, form by soft capsule content and soft capsule material, every soft capsule inner sealing is equipped with the content of 0.38g, described content is formed and mass ratio is: medicine: soybean oil: yellow beeswax=13: 24: 1, wherein, described medicine is that following three effective sites are amounted to into the mixing of crude drug amount by extraction ratio, its mass fraction ratio:

The extraction purification thing (yield: 6.59%): 7.77 parts of Radix Puerariae, Fructus Crataegi and Flos Carthami flavones ingredient

Arasaponin (7%): 1.26 parts

The Rhizoma Chuanxiong supercritical CO ₂Extract (5.385%): 0.98 part

The raw material components heavy amount mark proportioning of soft capsule material is: 1 part in gelatin, 0.45 part of glycerol, 0.8 part in water, 0.1 part of sorbitol, 0.06 part of citric acid, 0.01 part of titanium dioxide.

Manufacture method: make soft capsule content earlier, make the soft capsule material glue again, produce in the filling machine at soft capsule at last and be pressed into soft gelatin capsule.

Claims (3)

1. the Chinese patent medicine soft capsule Naodesheng is characterized in that, comprises soft capsule material and medicine, and medicine is formed mass percent and is: effective part group 20～35%: edible vegetable oil 57～72%: yellow beeswax 2～6%: lecithin 0～2.5%;

Described effective part group is that following three effective sites are amounted to into the mixing of crude drug amount by extraction ratio, and its ratio of quality and the number of copies is:

6～9 parts of Radix Puerariae, Fructus Crataegi and Flos Carthami extractive of general flavone

1～1.5 part of arasaponin

0.8～1.2 part of Rhizoma Chuanxiong oil;

Described vegetable oil comprises soybean oil, Oleum Brassicae campestris, Oleum Helianthi, Oleum Arachidis hypogaeae semen, siritch, the mixture of one or two or more kinds in Oleum sesami, Semen Maydis oil, the Oleum Gossypii semen.

2. Chinese patent medicine soft capsule Naodesheng as claimed in claim 1, it is characterized in that the raw material of soft capsule material and ratio of quality and the number of copies are: 1 part in gelatin, 0.3～0.6 part of glycerol, 0.05～0.15 part of sorbitol, 0.04～0.08 part of citric acid, 0.005～0.015 part of titanium dioxide, 1.1～1.3 parts in water.

3. the preparation method of the described Chinese patent medicine soft capsule Naodesheng of claim 1, raw material comprises: the extract of the total flavones of Radix Puerariae, Fructus Crataegi and Flos Carthami, Rhizoma Chuanxiong supercritical CO ₂The extract Rhizoma Chuanxiong oil, Radix Notoginseng total arasaponins, its feature formula comprises the steps:

1), by following ratio of quality and the number of copies weighting raw materials: 78 parts of Radix Notoginseng or commercially available Radix Notoginseng total arasaponins 2.73-5.46 part, 91 parts on Flos Carthami, 261 parts of Radix Puerariaes, 157 parts of enucleation Fructus Crataegis;

2), described Radix Puerariae, Fructus Crataegi and Flos Carthami are together got carried total flavones and get and carry thing, the extracting method step is: get Radix Puerariae, the mixing of Fructus Crataegi and Flos Carthami decoction pieces, the alcohol reflux three times that adds concentration 60-80%, for the first time the ethanol extraction of 10 times of amounts of dosing material amount is 2 hours, adds the ethanol extraction 1 hour of 8 times of amounts for the second time, adds the ethanol extraction 1 hour of 6 times of amounts for the third time, merge 3 times extracting solution, decompression recycling ethanol is concentrated to no ethanol flavor, must extract concentrated solution; Add water to every milliliter and contain crude drug 0.1 gram, filter, get filtrate; Filtrate is crossed the D-101 macroporous resin column adsorb, wash with water and ethanol elution, absorption, washing and ethanol elution process conditions are: the adsorption liquid flow velocity be 1-3 times of column volume/hour, absorption liquid measure be 4-5 times of column volume; The washing speed be 3 times of column volumes/hour, the washing volume be 4-6 times of column volume; The eluting concentration of ethanol is 30-60%, flow velocity be 1-3 times of column volume/hour, consumption is a 2-6 times of column volume; Collect ethanol elution, being concentrated into density is the 1.05-1.10 grams per milliliter, and spray drying obtains the extract that closes of Radix Puerariae, Fructus Crataegi and Flos Carthami 3 flavor Chinese medicines;

3), described Rhizoma Chuanxiong is extracted Rhizoma Chuanxiong oil, the extracting method step is: the Rhizoma Chuanxiong pulverizing medicinal materials is crossed 20 mesh sieves, places supercritical CO ₂Extract in the extraction equipment, extraction conditions is: 60 ℃ of extraction temperature, extracting pressure 35Mpa, 2 hours extraction time.Collect extract, the treated Rhizoma Chuanxiong oil that obtains;

4) with step 2) extractive of general flavone that obtains mixes with commercially available Radix Notoginseng total arasaponins, add edible vegetable oil, yellow beeswax, lecithin in proportion, the Rhizoma Chuanxiong oil mixing that obtains with step 3), make suspension, wherein material mass percentage ratio is: effective part group 20～35%: edible vegetable oil 57～72%: yellow beeswax 2～6%: lecithin 0～2.5%;

5) press ratio of quality and the number of copies, 1 part in gelatin, 0.3～0.6 part of glycerol, 0.05～0.15 part of sorbitol, 0.04～0.08 part of citric acid, 0.005～0.015 part of titanium dioxide and water are made glue for 1.1～1.3 parts;

6), the glue that obtains of suspension that step 4) is obtained and step 5) places the soft capsule production equipment to make soft capsule.

Images