CN101062157A - Process for preparing particles for Zhizhu - Google Patents
Process for preparing particles for Zhizhu Download PDFInfo
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- CN101062157A CN101062157A CN 200710022971 CN200710022971A CN101062157A CN 101062157 A CN101062157 A CN 101062157A CN 200710022971 CN200710022971 CN 200710022971 CN 200710022971 A CN200710022971 A CN 200710022971A CN 101062157 A CN101062157 A CN 101062157A
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- rhizoma atractylodis
- atractylodis macrocephalae
- fructus aurantii
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Abstract
The invention discloses a preparing craft of citrus atractylodes rhizome particle, which comprises the following steps: supercritical-extracting parched white atractylodes rhizome and parched citrus; getting extractive benzine; producing extract inclusion compound with beta-cyclodextrin; aqueous-extracting with medical slag of supercritical extract and lotus leaf; getting aqueous-extracting liquid; condensing with penetrate liquid of film separation; cubing with extract beta-cyclodextrin inclusion compound, right amount dextrin and sweet chrysanthemum glycosides boiling spray; getting the product. This particle possesses good curative effect and good stability.
Description
Technical field
The invention belongs to field of traditional Chinese medicine pharmacy, relate to the particulate preparation technology of a kind of trifoliate orange art.
Background technology
Trifoliate orange art granule is classical Chinese patent medicine, prescription derive from first Zhang Zhongjing " Medical Treasures of the Golden Chamber. aqueous vapor abnormal pulse card is also controlled " trifoliate orange art soup in the piece of writing, former side is made up of " seven pieces of Fructus Aurantii Immaturuss; two liang of the Rhizoma Atractylodis Macrocephalaes " two flavor medical materials, after the Jin Dynasty Zhang Yuansu is changed to Aurantii Immaturi and Atractylodis Pill, square by Fructus Aurantii Immaturus, the Rhizoma Atractylodis Macrocephalae, Folium Nelumbinis three flavor conventional Chinese medicines are formed, and are recorded in " medicine origin ".The disciple Zhang Dongyuan of Zhang Yuansu again this side is included in " differentiation on endogenous ", " Treatise on the spleen and stomach. diet impairment of the spleen opinion " and " secret record of the orchid chamber. the deficient opinion of taste " in, this medicine reasonable recipe, compatibility is simplified, determined curative effect, for treatment weakness of the spleen and stomach, lack of appetite do not change, gastral cavity abdomen feeling of fullness, clinical reflection effect is better." Chinese pharmacopoeia version in 1977 is recorded we at first, Aurantii Immaturi and Atractylodis Pill by name, and trifoliate orange art granules in 1993 dosage changing form on the former side of Aurantii Immaturi and Atractylodis Pill basis is a granule, lists national Chinese medicine in and protects the kind catalogue in 2003.Now, carry out quality control from the aspects such as content of character, moisture, melting, naringin according to traditional aqueous extraction-alcohol precipitation technology.But in the early stage production process, because production scale is little, reasons such as the source variation of medical material, with little test result gap is arranged: the rate of extract is very high in the production, and the moulding process that influences preparation is finished, and has influenced the realization of this product industrialized scale.
Rhizoma Atractylodis Macrocephalae (parched) is that the feverfew Rhizoma Atractylodis Macrocephalae (rhizome atractylodis macrocephalae) is through medical material behind the parched with bran.Have invigorating the spleen and benefiting QI, dampness diuretic, the antiabortive effect of hidroschesis, mainly contain volatile oil, lactone compound and polysaccharide.It is about 1.4% to contain volatile oil in Rhizoma Atractylodis Macrocephalae rhizome, and its main component is atractylone, atractylol etc., and wherein atractylone content in oil is 31.93%-61%, is usually used in insufficiency of the spleen lack of appetite clinically, and abdominal distention is had loose bowels, diseases such as phlegm retention vertigo and palpitation.Have the scholar to think, the atractylodes lactone constituents is Rhizoma Atractylodis Macrocephalae antiinflammatory, anticancer effective ingredient, and this constituents can be regulated gastrointestinal function and promote absorption of nutrient ingredients.We use the Rhizoma Atractylodis Macrocephalae behind the parched with bran, have research to think, extract excitatory reduces behind the Rhizoma Atractylodis Macrocephalae parched with bran, and the lactone composition increases, and has relaxed dry property simultaneously.Borrow during bran goes into, strengthen the effect of spleen invigorating, relieving distension.
Fructus Aurantii Immaturus (parched) is a medical material behind rutaceae Fructus Aurantii Immaturus (Fructus aurantii immaurus) the process parched with bran, and Fructus Aurantii Immaturus mainly contains volatile oil, flavone compound and Neosynephrine, N-methyltyramine etc.Clinically be usually used in treating food stagnation gastral cavilty feeling of fullness, stagnant constipation, diseases such as damp-heat dysentery.Flavones ingredient is mainly Hesperidin, and naringin, neohesperidin etc., this constituents can suppress the gastrointestinal smooth machine and shrink.Main component of essential oil is d-limonen, citral etc., and the extract constituents also has analgesia and antibacterial action except that suppressing the contraction of gastrointestinal smooth machine, and we use the Fructus Aurantii Immaturus behind the parched with bran.There is research to think that extract excitatory reduces behind the Fructus Aurantii Immaturus parched with bran, relaxes high strong property, exempt to hinder healthy energy, win with the eliminating stagnation painful abdominal mass power that disappears.
Contain multiple alkaloid and nelumboside, flavone, organic acid etc. in the Folium Nelumbinis, be used for summer-heat excessive thirst, diarrhea due to hypofunction of the spleen, hyperlipemia is also had better curative effect.Record in " the medical center bun is wanted ": " Folium Nelumbinis is gone into the liver branch more, and flat heat is dried, to go clearing heat in QI system.”
The traditional Chinese medical science is interpreted as this side's: in the side is monarch drug with the Rhizoma Atractylodis Macrocephalae, and invigorating the spleen for eliminating dampness is to help fortuneization; Fructus Aurantii Immaturus is a ministerial drug, and the therapeutic method to keep the adverse QI flowing downwards painful abdominal mass that disappears is removed full with intestinal stasis relieving; Folium Nelumbinis get to rise gastric qi, more, pull together with the Rhizoma Atractylodis Macrocephalae to cook and medicine, nourish essence derived from food and mend make stomach after.
A kind of extraction, isolation technics that supercritical liquid extraction technique (Supercritical Fluid Extraction is called for short SFE) rose in 20th century.The fifties in last century, the Todd of the U.S. and Elain have proposed its feasibility at first in theory, just are used for extracting and separating up to 70 o'clock age.(Supercritical Fluid SCF) is meant and is in critical temperature (T supercritical fluid
C) and critical pressure (P
C) above fluid, have gas, both characteristics of liquid concurrently: one, density approaches liquid, has the high density of similar liquids; Its two, viscosity and diffusion coefficient approach gas, have the low-viscosity of similar gas.So diffusion coefficient is 100 times of common liq.CO
2Polarity is little, is suitable for extracting materials such as little, the lipophilic extract of molecular weight, lactone, epoxide.And CO
2Stable in properties, nontoxic, nonflammable explosive, cheap and lower critical pressure (7.37MPa) and lower critical temperature (31.05 ℃) are used widely.
The influence factor of supercritical extraction has fluid ratio, the CO of SFE
2Flow, pressure, time, temperature, comminuted powder granularity etc.Pressure is most important parameter among the SFE.Under the uniform temperature, along with the increase of pressure, fluid density significantly increases, and the dissolubility of solute increases, and extraction efficiency improves.But too high pressure obviously improves production cost, and its extraction yield increases limited.In the SFE process, temperature increases, and has strengthened its diffusivity, makes extract at supercritical CO
2Middle dissolubility increases.Help extraction.But along with the increase of temperature, the dissolubility of impurity also increases, and makes subtractive process complicated, thereby reduces the yield of product.Simultaneous temperature increases, CO
2Fluidic density reduces, and makes to the dissolving power decline of solute, reduces product yield.The extraction time increases, and helps the dissolution equilibrium of effective ingredient in supercritical fluid and the solute, and the time that increases extraction just increases the extraction yield.Owing to behind the extraction certain hour, along with the minimizing of effective ingredient in the solute, increase the extraction time again, the extraction yield increases slowly, and energy consumption increases.And some invalid components also is extracted out more, directly influences the quality of product.
Membrane separation technique (Membrane Separation) is to utilize the thin film of selecting permeability is arranged, and is that motive force realizes the isolating technology of component of mixture with pressure.Membrane structure is divided into symmetric membrane, anisotropic membrane and composite membrane; Difference (or being called molecular cut off) according to its aperture can be divided into film micro-filtration membrane, ultrafilter membrane, NF membrane and reverse osmosis membrane; According to the difference of material, can be divided into inoranic membrane and organic membrane, inoranic membrane mainly also has only other film of microfiltration level, mainly is ceramic membrane and metal film.Organic membrane is made by macromolecular material, as cellulose family, polyamide-based, aromatic heterocycle class, polysulfones, TPO, silicone rubber kinds, fluoro containing polymers class etc.This technology can concentrate efficiently, enriched product, removes impurity effectively, and is easy to operate, non-secondary pollution.
The clathrate technology can make medicine peak time in vivo shorten, promote the medicine absorption in vivo, reaching peak concentration raises, improve bioavailability, and the medicine holdup time is in vivo shortened, and eliminate the half-life shortening, eliminate rapidly, medicine can be detained for a long time when reaching the curative effect of curing the disease in vivo, reduce side effect.
CN1363324 discloses the preparation method of nano medicine ' Zhishu ', adopt steps such as microwave extracting, concentrating under reduced pressure, supersonic jet technology spray drying, make new pharmaceutical preparation, its granularity reaches the 1200-1500 order, particle diameter 0.1-200nm, wherein most particle diameters are less than 100nm, and have new rerum natura.This preparation method and former Aurantii Immaturi and Atractylodis Pill preparation technique relatively improve a lot, but it is very crucial to choose extractant when adopting microwave extracting, and extracting substance must have absorption to microwave, and extraction container needs cooling, and this technology is not extracted at the volatility position in the trifoliate orange art side.Adopt supercritical extraction to extract, and adopt the beta-cyclodextrin inclusion compound technology to carry out enclose, can partly make full use of supercritical extraction at volatile component.
Summary of the invention
The purpose of this invention is to provide the particulate preparation technology of a kind of trifoliate orange art.
The objective of the invention is to realize by following technical measures:
The particulate preparation technology of a kind of trifoliate orange art, the weight portion of selecting raw medicinal material for use is 40 parts of Rhizoma Atractylodis Macrocephalae (parched)s, 20 parts of Fructus Aurantii Immaturus (parched), 6 parts on Folium Nelumbinis, this technology may further comprise the steps:
A, weighting raw materials Rhizoma Atractylodis Macrocephalae (parched) by weight ratio, Fructus Aurantii Immaturus (parched), Folium Nelumbinis, standby;
B, pulverizing: Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) are pulverized, mix homogeneously, standby;
C, supercritical extraction: get Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) hybrid particles in extraction kettle, CO
2Supercritical extraction, extracting pressure are 30-36Mpa, and the extraction kettle temperature is 40-60 ℃, CO
2Flow velocity is 24～30L/h, and the extraction time is 0.5-2.5 hour, collects extract, and is standby;
D, water are carried: CO learns from else's experience
2Rhizoma Atractylodis Macrocephalae (parched) that supercritical extraction is crossed and Fructus Aurantii Immaturus (parched) medicinal residues, Folium Nelumbinis add 6～10 times of water gagings and decoct 1～3 time, and each 1～3 hour, filter, merging filtrate gets the water extract;
E, membrance separation: after the water extract adopts the aperture to be the membrane filtration in 0.2 μ m aperture earlier, the membrane filtration in filtrate reuse 0.01 μ m aperture; The clear paste that it is 1.10-1.20 that permeate is evaporated to 60 ℃ of relative densities, standby;
F, extract enclose: get the beta-schardinger dextrin-that the 6-10 of extract weight doubly measures, the water that the 2-4 of adding beta-schardinger dextrin-amount doubly measures grinds well, pour in the colloid mill, slowly drip the extract with dissolve with ethanol continuously, pure consumption is the 15%-45% of extract volume, milled enclose 30-50 minute, inclining, and cold preservation was left standstill 12～48 hours, filters, in 40 ℃ of vacuum dryings, promptly get the extract clathrate;
G, granulation: extract clathrate and an amount of dextrin, stevioside mix, and put in the pellet fabrication device, and clear paste is sprayed into, and one time inlet temperature is 70-90 ℃; The secondary air temperature is 90-110 ℃; Leaving air temp is 40-50 ℃, and temperature of charge: 50-80 ℃, peristaltic pump rotating speed: 60-120r/min, gained granule are trifoliate orange art granule.
Described preparation technology, wherein the film that adopts among the step e is an inorganic ceramic film.
Described preparation technology, middle Rhizoma Atractylodis Macrocephalae (parched) is the Rhizoma Atractylodis Macrocephalae behind the parched with bran, Fructus Aurantii Immaturus (parched) is the Fructus Aurantii Immaturus behind the parched with bran.
Beneficial effect of the present invention:
In the trifoliate orange art granule technology provided by the invention, advanced technologies such as supercritical extraction technique, membrane separation technique, beta-cyclodextrin inclusion compound technology have been used, and adopting statistics experimental technique optimization extraction and preparation technology, the trifoliate orange art granule that adopts prepared of the present invention is lower than trifoliate orange art granule the rate of extract of prior art for preparing, good effect, good stability.
Adopt different preparation technologies at different raw materials in this technology, make the effective site of each raw material can access abundant application, be embodied in the following aspects:
(1) Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) CO
2The research of supercritical extraction process
1, orthogonal test is selected supercritical CO by the trial test result
2The factor that the extract yield has the greatest impact: extracting pressure, extraction temperature, CO
2Flow and extraction time, use Orthogonal Experiment and Design table L
9(3
4) carrying out the screening of best extraction process, get it filled material Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) mixed powder 400g (cross sieve No. 3, wherein the weight ratio of Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) is 2: 1, down with) they are evaluation index with extraction yield (%), test arrangement and the results are shown in Table 1-3.
Table 1 orthogonal test factor level table
| Level | Factor | |||
| A extracting pressure (MPa) | The B extraction temperature (℃) | C CO 2Flow (L/h) | D extracts the time (min) | |
| 1 | 30 | 40 | 24 | 30 |
| 2 3 | 33 36 | 50 60 | 27 30 | 45 60 |
Arrangement of table 2 orthogonal test and table as a result
| Tested number | A | B | C | D | Extract yield (%) |
| 1 2 3 4 5 6 7 8 9 I j II j III j I j/3 II j/3 III j/3 R | 1 1 1 2 2 2 3 3 3 7.829 8.826 8.492 2.61 2.942 2.831 0.332 | 1 2 3 1 2 3 1 2 3 9.454 7.059 8.634 3.151 2.353 2.878 0.798 | 1 2 3 2 3 1 3 1 2 6.928 10.007 8.212 2.309 3.336 2.737 1.026 | 1 2 3 3 1 2 2 3 1 6.654 9.195 9.298 2.218 3.065 3.099 0.881 | 1.906 2.981 2.942 4.146 1.868 2.812 3.402 2.210 2.880 ∑＝25.147 C 1＝70.264 |
Table 3 analysis of variance table
| Soruces of variation | Sum of sguares of deviation from mean | Degree of freedom | Mean square | F | P |
| B C D A amounts to | 1.197 1.903 1.676 0.268 5.044 | 2 2 2 2 8 | 0.598 0.952 0.838 0.134 | 4.47 7.108 6.261 | ＞0.05 ＞0.05 ＞0.05 |
F
0.05(2，2)＝19.00
By intuitive analysis, R value C＞D＞B＞A, factor C is to supercritical CO
2The influence of extract yield is big slightly, is CO according to the size order that influences to yield promptly
2Flow, extraction time, extraction temperature, extracting pressure.The extraction conditions of best of breed is A
2B
1C
2D
3, promptly extracting pressure is 33Mpa, extraction temperature is 40 ℃, CO
2Flow is 27L/h, and the extraction time is 60 minutes.Variance analysis learns, each factor is thought by analysis and respectively organized parameter within preferable scope through what set after the trial test result's there are no significant influence.
2, demonstration test is in order to verify the feasibility of orthogonal test, getting Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) mixed powder 400g, carry out 3 batches of demonstration tests according to above-mentioned optimum process condition, serves as to investigate index with extraction yield (%), three batches of average extraction yields of test are 4.27%, show that this process stabilizing is feasible.
(2) membrance separation trifoliate orange art granule water is put forward the technical study of solution each several part
1, the preparation of water extract
Above-mentioned CO learns from else's experience
2Rhizoma Atractylodis Macrocephalae (parched) that supercritical extraction is crossed and Fructus Aurantii Immaturus (parched) medicinal residues, Folium Nelumbinis medical material add 6～10 times of water gagings and decoct 1～3 time, and each 1～3 hour, filter, merging filtrate gets the water extract.
2, test method
A certain amount of feed liquid is poured in the storage tank, adopt intrinsic pressure cross flow filter mode, configure operating pressure and operative temperature (along with the time increases, temperature progressively rises), constant flow pump will place the feed liquid circulation of storage tank to squeeze into the membrane module cross flow filter, penetrating fluid is flowed out by the assembly side exit, and the liquid stream that dams returns storage tank, and flow velocity and filtration pressure difference are controlled by valve.
3, result of the test
The rate of extract is about 28% behind the trifoliate orange art granule original production process water extract-alcohol precipitation, and the inorganic ceramic film the rate of extract that adopts 0.01 μ m aperture is 17.26, and the rate of extract has reduced by 10 percentage points.The result sees table 4 for details
Table 4 membrane separation process separates the rate of extract at each position
| Sequence number | Membrane material | Film type | Kpattern number | Nib footpath (μ m) | Molecular weight (* 10 dams 3) | Advance film pressure (MPa) | Temperature (℃) | The rate of extract (%) |
| 1 2 3 4 5 6 | Inorganic ceramic film inorganic ceramic film organic membrane (polysulfones) organic membrane (polysulfones) organic membrane (polysulfones) inorganic ceramic film | Rolling rolling rolling rolling rolling rolling | - - 1623 1623-0711 0711 - | 0.2 0.2-0.01 - - - 0.01 | - - 20-10 10-3 3 20 | 0.12 0.21 0.80 - 2.00 0.21 | 32 30 34 30 31 30 | 7.6 2.30 10.92 3.64 2.70 17.26 |
Because the disposable use of organic membrane, the cost height is not paid the utmost attention in the commercial production, and inorganic ceramic film has high thermal stability, resistance to chemical attack, no problem of aging, long service life, characteristics such as can anti-phasely wash, the preferred inorganic ceramic film of the present invention.By experiment the result as can be known, using the aperture is that position the rate of extract that 0.01 μ m inorganic ceramic film dams has only 17.26%, reduces by 10 percentage points than former technology the rate of extract, is suitable for preparation.So after selecting for use the aperture to be the inorganic ceramic film elimination float of 0.2 μ m earlier, select for use 0.01 μ m inorganic ceramic film to dam again, permeate is required medicinal liquid.
(3) Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract beta-cyclodextrin inclusion compound technical study
The method of beta-cyclodextrin inclusion compound has saturated water solution method, and ultrasonic method and grinding method are considered factors such as the physicochemical property of Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract and industrialization, select for use colloid milling to carry out the research of beta-cyclodextrin inclusion compound.The principal element that influences the enclose effect has host and guest's molecular proportion, adds water and doubly measures, and enclose time and pure consumption carry out enclose to Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract.
1, the research of Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract beta-cyclodextrin inclusion compound technology
Orthogonal test is got above-mentioned Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract 10g, adopts L
9(3
4) orthogonal array, with clathrate yield, clathrate oil utilization rate, clathrate oil content is evaluation index, and employing comprehensive grading method, (clathrate yield, clathrate oil utilization rate, clathrate oil content three weight coefficient are respectively 0.2,0.4,0.4), preferred optimised process.Quadrature factor level table sees Table 5.
Table 5 Fructus Aurantii Immaturus (parched) and Rhizoma Atractylodis Macrocephalae (parched) supercritical extract enclose quadrature factor level table
| Level | Factor | |||
| A extract: beta-schardinger dextrin-(g: g) | The B enclose time (min) | C adds water and doubly measures (doubly) | D alcohol consumption (%) | |
| 1 2 3 | 1∶6 1∶8 1∶10 | 30 40 50 | 2 3 4 | 15 30 45 |
This experiment adopts the aggregative weighted point system to carry out data analysis in order to consider the problem of several indexs simultaneously, and promptly changing many indexs is that single index is analyzed.If clathrate yield, clathrate oil utilization rate, clathrate oil content three weight coefficient are respectively 0.2,0.4,0.4, three best indexs all are decided to be 100 fens, to clathrate comprehensive grading statistical analysis as a result.By variance analysis as can be known, each factor is arranged as C＞A＞B＞D to the size that influences of this index, and A and C factor have significant difference, and establishing the enclose optimised process is A
2B
3C
3D
3Consider the yield of clathrate and oil content this two indexs and production cost of clathrate, the enclose optimum condition is: Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) mixed extracts: beta-schardinger dextrin-is 1: 8 (weight ratio), and grinding time is 50min, 4 times of amounts of amount of water, alcohol adding amount is 45%.
2, demonstration test is in order to verify whether best clathrate process conforms to orthogonal experiments, carry out 3 batches of demonstration tests by preferred optimised process, get Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract 10g, with the oil content is to investigate index, the checking result is: clathrate yield 96.1 (%), oily utilization rate 96.9 (%), oil content 14.5 (%), confirm to conform to substantially, so determine that optimum process condition is A with the quadrature result
2B
3C
3D
3Be Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) mixed extracts: beta-schardinger dextrin-is 1: 8 (weight ratio), and grinding time is 50min, 4 times of amounts of amount of water, and alcohol adding amount is 45%.
(4) boiling spray-drying process
Adopt boiling spray drying one-step palletizing technology, be characterized in integrating spray drying, airpillow-dry and fluidization, realize the granulation of liquid material one-step method, particle diameter 0.2-2mm.It is good to have mobility of particle, and the granule melting is good, and disposable finished product increases substantially, and can reach more than 90% advantages such as minimizing in man-hour.Also be fit to extractum and adjuvant simultaneously than little kind, through above-mentioned technology, yield of extract descends and can reach about 10%, but conventional method of granulating is that certain degree of difficulty is arranged, and therefore selects for use boiling spray drying one-step palletizing technology to have certain advantage.
1, boiling spray-drying process method
Stevioside, dextrin and the cyclodextrin clathrate mixed accessories of pulverizing 120 mesh sieves are thrown on the airflow-distribution board of people's fluidized bed granulation chamber, started aerator, the hot blast of making a gift to someone, make the adjuvant preheating, when room temperature reaches predetermined temperature, start the spraying button, will extract concentrated solution and spray into.After spray granulation was finished, continuing to ventilate made grain fluidized dry certain hour, promptly.
2, the selection of spray drying condition and spraying result
2.1 selection of process parameters
Inlet temperature, medicinal liquid pressure (peristaltic pump rotating speed) are important parameters, because particle temperature is a basic fixed, leaving air temp is determined by inlet temperature, two combined factors effects of medicinal liquid pressure, inlet temperature is limited by equipment performance, select big as far as possible parameter setting for use, with the 5kg granule is experiment sample, selects the peristaltic pump rotating speed as controlling index.Comprehensive production efficiency and yield rate screening optimal processing parameter.Peristaltic pump rotating speed speed is bigger to the production efficiency influence, and yield rate is also had certain influence, because speed is fast, grain diameter is big, and then particle diameter is less slowly for speed.The results are shown in Table 6.
Table 6 boiling spray granulation technological parameter The selection result
| Sequence number | Inlet temperature (℃) | The secondary air temperature (℃) | Peristaltic pump rotating speed (r/min) | Production efficiency (man-hour) | Yield rate (%) |
| 1 2 3 | 70-90 70-90 70-90 | 90-110 90-110 90-110 | 60-90 60-120 60-150 | 5 3.5 2 | 85 92 76 |
2.2 moulding process index
Extract clathrate and an amount of dextrin, stevioside mix, and put in the boiling spray granulation device, and clear paste is sprayed into.One time inlet temperature is 70-90 ℃; The secondary air temperature is 90-110 ℃; Leaving air temp is 40-50 ℃.Temperature of charge :≤60 ℃, peristaltic pump rotating speed: 60-120r/min.
2.3 demonstration test
All meet the requirements by the every index of its granule of above-mentioned technology, can better obtain granulating efficiency.The result sees table 7 for details
Table 7 boiling spray granulation technological parameter checking result
| Sequence number | Inlet temperature (℃) | The secondary air temperature (℃) | Peristaltic pump rotating speed (r/min) | Production efficiency (man-hour) | Yield rate (%) |
| 1 2 3 | 70-90 70-90 70-90 | 90-110 90-110 90-110 | 60-120 60-120 60-120 | 3.5 3.5 3.5 | 93 92 90 |
Pharmacodynamic experiment of the present invention:
This experimentation trifoliate orange art granule (new technology) (making by embodiment 1) confirms its main pharmacodynamics effect to the propulsive function effect of gastric emptying intestinal.Animal is adopted mice, and dosage is 3.96g (crude drug amount)/kg in the set dosage, and each separated part of trifoliate orange art granule (obtaining with different membrane aperture separation) dosage is equivalent to dosage 19.8g (crude drug amount)/kg in the former technology of trifoliate orange art granule.
Be subjected to the reagent thing:
Molecular weight is greater than 200,000: the 0.2 μ m inorganic ceramic film part of damming
Molecular weight 200,000-20,000: after 0.2 μ m inorganic ceramic film filters, the part that permeation parts is dammed through 0.01 μ m inorganic ceramic film again
Molecular weight is less than 20,000: directly through 0.01 μ m inorganic ceramic film permeation parts
Molecular weight 20,000-10,000: after 0.01 μ m inorganic ceramic film filters, the part that permeation parts is dammed through 1623 type organic membrane again
Molecular weight 10,000-3000:1623 type organic membrane filters the part that the back permeation parts is dammed through 0711 type organic membrane again
Molecular weight sees through the position less than 3000:0711 type organic membrane
Former technology extractum: produce lot number: 060601 by Nanjing Zhongshan Pharmaceutical Co., Ltd.
Supercritical CO
2Extraction Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) mixed extracts
Supercritical CO
2Extraction back Rhizoma Atractylodis Macrocephalae (parched) medicinal residues water extract;
Supercritical CO
2Extraction back Fructus Aurantii Immaturus (parched) medicinal residues water extract;
Folium Nelumbinis single medical material water extract
The foundation of 1 animal model and test method
1.1 animal grouping
Each effect experiment is according to being divided into groups by the reagent thing, is set at matched group (0.5%CMC-Na), positive drug group (dicetel), respectively is subjected to reagent thing group.
1.2 the foundation of model
1.2.1 spleen deficiency animal model
Get 100% Radix Et Rhizoma Rhei decocting liquid (1g/ml), gavage by 0.8ml/ consumption only, once a day, continuous 7 days.
1.2.2 food stagnation disease animal model
Get special high protein feed and feed, test the milk powder solution that added hello 25wt% concentration on the 1st, each 0.7ml/, every day twice, continuous 7 days.
1.3 small intestinal charcoal end advances experiment
Get kunming mice, by the body weight random packet, be divided into matched group (0.5%CMC-Na), positive drug group (dicetel), respectively be subjected to reagent thing group, adopt small intestinal charcoal end propulsion trial, gastric infusion or equal-volume distilled water are 7 days continuously, and each is organized dosage and converts by body surface area, the per 10 gram body weight administration 0.2ml of mice, fasting was freely drunk water 24 hours, carried out the intestinal propulsion trial on the 8th day.The blank group is irritated stomach with distilled water 0.2ml/10g, and other group is irritated and raised relative medicine 0.2ml/10g respectively, and behind the 30min, each group is irritated stomach with charcoal end paste 0.2ml/20g body weight.Took off cervical vertebra execution in 20 minutes after the administration, open the abdominal cavity and separate mesentery, the clip upper end is to pylorus, and lower end to the intestinal tube of ileocecus places on the pallet.Gently small intestinal is pulled into straight line, measure intestinal tube length as " small intestinal total length ".The distance in forward position, end is as " the charcoal end is at the enteral advance distance " from pylorus to charcoal.Calculate the charcoal end with formula and advance percentage rate.
With matched group relatively and carry out t check.
1.4 emptying test
Difference according to the weight of animals, random packet, be divided into matched group (0.5%CMC-Na), positive drug group (dicetel), respectively be subjected to reagent thing group (Chinese medicine composition of the present invention), gastric infusion or equal-volume distilled water are 7 days continuously, each is organized dosage and converts by body surface area, the per 10 gram body weight administration 0.2ml of mice, fasting was freely drunk water 24 hours, carried out the intestinal propulsion trial on the 8th day.The blank group is irritated stomach with distilled water 0.2ml/10g, and other group is irritated and raised relative medicine 0.2ml/10g respectively, and each group is irritated and only raised the semi-solid 0.8ml/ of paste behind the 30min.Take off cervical vertebra behind the 20min and put to death animal, cut the abdominal cavity open, ligation stomach cardia, pylorus and distal small intestine are taken out stomach.And wipe away with filter paper and to do the back and claim full weight, cut off body of stomach along greater gastric curvature then, wipe away driedly behind the flush away gastric content, claim net weight.Calculate gastric emptying rate (%), each experimental group gastric emptying rate average and matched group are relatively and carry out t and check.Computing formula is as follows:
Gastric emptying rate (%)=1-gastric food survival rate
Wherein consume unwise following: put to death immediately after gavaging semi-solid paste with normal mouse, method is the same, claims stomach full weight, stomach net weight, is calculated as follows: the semi-solid paste of consumption mistake=(stomach full weight-stomach net weight)-0.8ml is heavy
2, insufficiency of the spleen group of mice gastric emptying intestinal advanced experiment
Set up the spleen deficiency animal model, mice with spleen deficiency is carried out gastric emptying and intestinal propulsion trial, result of the test shows that mice with spleen deficiency small intestinal charcoal end propelling rate and gastric emptying rate all are lower than the normal control group, and group difference is (P＜0.05) significantly, and the modeling success is described.Except Folium Nelumbinis medical material water extract group, other each groups more all have significant difference with model group.Particularly molecular weight is less than 20,000 components and supercritical extraction component and model group comparing difference highly significant (P＜0.001).Fructus Aurantii Immaturus (parched) and Rhizoma Atractylodis Macrocephalae (parched) supercritical extract part relatively have significant difference (P＜0.05) with former process portion, and molecular weight compares no significant difference (P＞0.05) less than 3000 short insufficiency of the spleen group of mice gastric emptying intestinal propelling rate of component and former technology group.Take all factors into consideration, under the identical dosage, the position of trifoliate orange art granule small-molecular weight and supercritical extraction position curative effect are better than the former technology of trifoliate orange art granule.Experimental result the results are shown in Table 8-9 to advance percentage rate (%) expression.T-student check between statistics employing group.
The influence of table 8 pair mice with spleen deficiency small intestinal charcoal end propulsion functions (X ± S)
| Group | Dosage (g/kg) | Animal (only) | Advance percentage rate (%) |
| Blank group (A group) model group (B group) positive controls (C group) molecular weight greater than 200,000 groups of (D group) molecular weight 200,000-20,000 (E group) molecular weight 20,000-10,000 (F group) molecular weight 10,000-3000 (G group) molecular weight less than 3000 (H group) molecular weight less than the former technology groups of 20,000 (I groups) (J group) rhizoma atractylodis macrocephalae with fry the overcritical mixed extracts group of the dried immature fruit of citron orange (K group) supercritical CO2Extraction back Rhizoma Atractylodis Macrocephalae (parched) medicinal residues water extract groups (L group) supercritical CO 2Extraction back Fructus Aurantii Immaturus (parched) medicinal residues water extract groups (M group) Folium Nelumbinis medical material water extract groups (N group) | 1.35 1.35 0.03 1.35 1.35 1.35 1.35 1.35 1.35 1.128 0.0609 1.8 1.31 0.37 | 10 10 10 10 10 10 10 10 10 10 10 10 10 10 | 57±6.41 *# 49±5.37 ### 62±8.12 ** 56±6.44 *# 62±7.79 ** 65±9.11 *** 62±6.32 ** 69±5.55 *** 70±6.53 *** 63±7.41 ** 71±8.21 ***# 60±7.98 ** 67±5.47 *** 54±6.83 # |
Compare with the B group
*P＜0.05
*P＜0.01
* *P＜0.001
Compare with the J group
#P＜0.05
##P＜0.01
###P＜0.001
The influence of table 9 pair mice with spleen deficiency gastric emptying (X ± S)
| Group | Dosage (g/kg) | Animal (only) | Advance percentage rate (%) |
| Blank group (A group) model group (B group) positive controls (C group) molecular weight is greater than 200,000 groups of (D group) molecular weight 200,000-20,000 (E group) | 1.35 1.35 0.03 1.35 1.35 | 10 10 10 10 10 | 50±3.37 *# 42±7.81 ## 55±4.67 ** 48±5.56 ## 46±4.89 ## |
| Molecular weight 20,000-10,000 (F group) molecular weight 10,000-3000 (G group) molecular weight less than 3000 (H group) molecular weight less than the former technology groups of 20,000 (I groups) (J group) rhizoma atractylodis macrocephalae with fry the overcritical mixed extracts group of the dried immature fruit of citron orange (K group) supercritical CO2Extraction back Rhizoma Atractylodis Macrocephalae (parched) medicinal residues water extract groups (L group) supercritical CO 2Extraction back Fructus Aurantii Immaturus (parched) medicinal residues water extract groups (M group) Folium Nelumbinis medical material water extract groups (N group) | 1.35 1.35 1.35 1.35 1.128 0.0609 1.8 1.31 0.37 | 10 10 10 10 10 10 10 10 10 | 58±4.90 *** 56±6.31 ** 60±8.42 *** 59±7.33 *** 59±5.73 *** 68±1.23 ***# 60±5.67 *** 62±1.30 *** 48±5.32 ## |
Compare with the B group
*P＜0.05
*P＜0.01
* *P＜0.001
Compare with the J group
#P＜0.05
##P＜0.01
###P＜0.001
3, food stagnation mice gastric emptying intestinal is advanced experiment
Set up food stagnation disease animal model, the food stagnation mice is carried out gastric emptying and intestinal propulsion trial, result of the test shows: food stagnation mice gastric emptying and small intestinal charcoal end propelling rate are lower than normal control group (P＜0.05).Except Folium Nelumbinis medical material water extract group, other each groups and model group all have significant difference relatively to food stagnation mice intestinal propelling rate.Fructus Aurantii Immaturus (parched) and Rhizoma Atractylodis Macrocephalae (parched) supercritical extract part relatively have significant difference (P＜0.05) to food stagnation mice intestinal propelling rate and former process portion.Be that molecular weight is less than 3000 groups and mixed extracts group and Fructus Aurantii Immaturus medicinal residues group and model group difference highly significant (P＜0.001).Take all factors into consideration, under the identical dosage, trifoliate orange art granulin molecule amount is better than the former technology of trifoliate orange art granule less than 20,000 position and supercritical extraction position curative effect.Experimental result the results are shown in Table 10-11 to advance percentage rate (%) expression.T-student check between statistics employing group.
The influence of table 10 pair food stagnation mouse small intestine charcoal end propulsion functions (X ± S)
| Group | Dosage (g/kg) | Animal (only) | Advance percentage rate (%) |
| Blank group (A group) model group (B group) positive controls (C group) molecular weight greater than 200,000 groups of (D group) molecular weight 200,000-20,000 (E group) molecular weight 20,000-10,000 (F group) molecular weight 10,000-3000 (G group) molecular weight less than 3000 (H group) molecular weight less than the former technology groups of 20,000 (I groups) (J group) rhizoma atractylodis macrocephalae with fry the overcritical mixed extracts group of the dried immature fruit of citron orange (K group) supercritical CO2Extraction back Rhizoma Atractylodis Macrocephalae (parched) medicinal residues water extract groups (L group) supercritical CO 2Extraction back Fructus Aurantii Immaturus (parched) medicinal residues water extract groups (M group) Folium Nelumbinis medical material water extract groups (N group) | 1.35 1.35 0.03 1.35 1.35 1.35 1.35 1.35 1.35 1.128 0.0609 1.8 1.31 0.37 | 10 10 10 10 10 10 10 10 10 10 10 10 10 10 | 62±6.33 *# 54±7.66 ### 67±5.45 ** 59±4.99 ## 60±7.65 ## 63±8.24 * 67±5.57 ** 77±6.83 ***# 70±8.13 *** 69±6.23 *** 79±5.18 ***# 68±2.83 *** 73±5.61 *** 60±6.22 ## |
Compare with the B group
*P＜0.05
*P＜0.01
* *P＜0.001
Compare with the J group
#P＜0.05
##P＜0.01
###P＜0.001
The influence of table 11 pair food stagnation mice gastric emptying (X ± S)
| Group | Dosage (g/kg) | Animal (only) | Advance percentage rate (%) |
| Blank group (A group) model group (B group) positive controls (C group) molecular weight greater than 200,000 groups of (D group) molecular weight 200,000-20,000 (E group) molecular weight 20,000-10,000 (F group) molecular weight 10,000-3000 (G group) molecular weight less than 3000 (H group) molecular weight less than the former technology groups of 20,000 (I groups) (J group) rhizoma atractylodis macrocephalae with fry the overcritical mixed extracts group of the dried immature fruit of citron orange (K group) supercritical CO2Extraction back Rhizoma Atractylodis Macrocephalae (parched) medicinal residues water extract groups (L group) supercritical CO 2Extraction back Fructus Aurantii Immaturus (parched) medicinal residues water extract groups (M group) Folium Nelumbinis medical material water extract groups (N group) | 1.35 1.35 0.03 1.35 1.35 1.35 1.35 1.35 1.35 1.128 0.0609 1.8 1.31 0.37 | 10 10 10 10 10 10 10 10 10 10 10 10 10 10 | 42±2.24 *### 35±2.56 ### 49±7.56 ***## 41±2.42 ### 42±5.79 *### 50±6.77 ***## 47±5.32 **### 59±4.78 *** 69±3.56 ***# 62±4.88 *** 63±6.21 *** 47±7.98 *### 51±5.47 ***## 42±6.83 *### |
Compare with the B group
*P＜0.05
*P＜0.01
* *P＜0.001
Compare with the J group
#P＜0.05
##P＜0.01
###P＜0.001
4. Test Summary
Except Folium Nelumbinis, the small-molecule substance of single medical material, former handicraft product and membrance separation can both promote the mice gastrointestinal motility, but the micromolecule position more remarkable effect that membrance separation goes out.In addition, compare with former technology extractum, molecular weight is not obvious greater than each position drug effect of 20,000, molecular weight is strong slightly for promotion mice gastric emptying and intestinal propulsion functions less than 20,000 position and supercritical extraction mixing medical material position, illustrates that the isolated micromolecule of new technology position drug effect and former technology more do not reduce.And the former average efficacy result is better than the latter.Investigated single medicinal material slag water extract simultaneously and promoted gastric emptying and intestinal propulsion functions, single Fructus Aurantii Immaturus effect is better than the single Rhizoma Atractylodis Macrocephalae, but is not so good as compound recipe in conjunction with the animal model effect.This experiment illustrates the important of drug matching harmony on the one hand, determines that on the other hand compound effective component is at micromolecule position and volatility position.
The specific embodiment
The invention will be further elaborated by the following examples.
Press 100g calculating for every part in following examples.
Embodiment 1
Get 40 parts of Rhizoma Atractylodis Macrocephalae (parched)s, 20 parts of Fructus Aurantii Immaturus (parched), 6 parts on Folium Nelumbinis, adopt the following steps preparation:
(1) pulverize: Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) are ground into 20 purpose coarse powder, standby.
(2) CO
2Supercritical extraction: get Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) mixing coarse powder in extraction kettle, heating extraction kettle and extraction-container reach predetermined temperature, send into the CO of certain flow rate
2Gas begins cycling extraction after regulating each still pressure, and wherein the extraction kettle temperature is 60 ℃, and pressure is 36Mpa, CO
2Flow velocity is 27L/h, and the extraction time is 0.5 hour, and extract is standby in the collection separating still.
(3) water is carried: CO learns from else's experience
2Rhizoma Atractylodis Macrocephalae (parched) that supercritical extraction is crossed and Fructus Aurantii Immaturus (parched) medicinal residues, Folium Nelumbinis medical material add 8 times of water gagings and decoct 2 times, and each 2 hours, filter, merging filtrate gets the water extract.
(4) membrance separation: after the water extract adopts the aperture to be the inorganic ceramic membrane filtration in 0.2 μ m aperture earlier, the inorganic ceramic membrane filtration in filtrate reuse 0.01 μ m aperture.It is 1.20 clear paste that permeate is evaporated to 60 ℃ of relative densities, standby.
(5) extract enclose: the beta-schardinger dextrin-of getting 8 times of amounts of extract weight, the water that adds 3 times of amounts of beta-schardinger dextrin-weight grinds well, pour in the colloid mill, slowly drip Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract with dissolve with ethanol continuously, pure consumption is 45% of an extract volume, mills 60 minutes, incline to, cold preservation was left standstill 12 hours, in 40 ℃ of vacuum dryings, promptly got the extract clathrate.
(6) granulate: extract clathrate and an amount of dextrin, stevioside mix, and put in the boiling spray granulation device, and clear paste is sprayed into.One time inlet temperature is 90 ℃; The secondary air temperature is 90 ℃; Leaving air temp is 50 ℃.Temperature of charge: 60 ℃, peristaltic pump rotating speed: 120r/min, gained granule are trifoliate orange art granule.
(7) fill:, carry out fill, promptly with the gained granule.
Embodiment 2
Get 40 parts of Rhizoma Atractylodis Macrocephalae (parched)s, 20 parts of Fructus Aurantii Immaturus (parched), 6 parts on Folium Nelumbinis, adopt the following steps preparation:
(1) pulverize: Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) are ground into 40 purpose fine powders, standby.
(2) CO
2Supercritical extraction: get Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) mixing fine powders in extraction kettle, heating extraction kettle and extraction-container reach predetermined temperature, send into the CO of certain flow rate
2Gas begins cycling extraction after regulating each still pressure, and wherein the extraction kettle temperature is 40 ℃, and pressure is 30Mpa, CO
2Flow velocity is 24L/h, and the extraction time is 1.0 hours.
(3) water is carried: CO learns from else's experience
2Rhizoma Atractylodis Macrocephalae (parched) that supercritical extraction is crossed and Fructus Aurantii Immaturus (parched) medicinal residues, Folium Nelumbinis medical material add 10 times of water gagings and decoct 1 time, and each 3 hours, filter, merging filtrate gets the water extract.
(4) membrance separation: after the water extract adopts the aperture to be the inorganic ceramic membrane filtration in 0.2 μ m aperture earlier, the inorganic ceramic membrane filtration in filtrate reuse 0.01 μ m aperture.It is 1.10 clear paste that permeate is evaporated to 60 ℃ of relative densities, standby.
(5) extract enclose: the beta-schardinger dextrin-of getting 7 times of amounts of extract weight, the water that adds 2 times of amounts of beta-schardinger dextrin-weight grinds well, pour in the colloid mill, slowly drip Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract with dissolve with ethanol continuously, pure consumption is 30% of an extract volume, mills 30 minutes, incline to, cold preservation was left standstill 24 hours, in 40 ℃ of vacuum dryings, promptly got the extract clathrate.
(6) granulate: extract clathrate and an amount of dextrin, stevioside mix, and put in the boiling spray granulation device, and clear paste is sprayed into.One time inlet temperature is 70 ℃; The secondary air temperature is 100 ℃; Leaving air temp is 40 ℃.Temperature of charge: 70 ℃, peristaltic pump rotating speed: 110r/min, gained granule are trifoliate orange art granule.
(7) fill:, carry out fill, promptly with the gained granule
Embodiment 3
Get 40 parts of Rhizoma Atractylodis Macrocephalae (parched)s, 20 parts of Fructus Aurantii Immaturus (parched), 6 parts on Folium Nelumbinis, adopt the following steps preparation:
(1) pulverize: Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) are ground into 60 purpose fine powders, standby.
(2) CO
2Supercritical extraction: get Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) fine powder in extraction kettle, heating extraction kettle and extraction-container reach predetermined temperature, send into the CO of certain flow rate
2Gas begins cycling extraction after regulating each still pressure, and wherein the extraction kettle temperature is 50 ℃, and pressure is 33Mpa, CO
2Flow velocity is 30L/h, and the extraction time is 0.75 hour.
(3) water is carried: CO learns from else's experience
2Rhizoma Atractylodis Macrocephalae (parched) that supercritical extraction is crossed and Fructus Aurantii Immaturus (parched) medicinal residues, Folium Nelumbinis medical material add 6 times of water gagings and decoct 3 times, and each 1 hour, filter, merging filtrate gets the water extract.
(4) membrance separation: after the water extract adopts the aperture to be the inorganic ceramic membrane filtration in 0.2 μ m aperture earlier, the inorganic ceramic membrane filtration in filtrate reuse 0.01 μ m aperture.It is 1.15 clear paste that permeate is evaporated to 60 ℃ of relative densities, standby.
(5) extract enclose: the beta-schardinger dextrin-of getting 6 times of amounts of extract weight, the water that adds 4 times of amounts of beta-schardinger dextrin-weight grinds well, pour in the colloid mill, slowly drip Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract with dissolve with ethanol continuously, pure consumption is 15% of an extract volume, mills 50 minutes, incline to, cold preservation was left standstill 36 hours, in 40 ℃ of vacuum dryings, promptly got the extract clathrate.
(6) granulate: extract clathrate and an amount of dextrin, stevioside mix, and put in the boiling spray granulation device, and clear paste is sprayed into.One time inlet temperature is 80 ℃; The secondary air temperature is 110 ℃; Leaving air temp is 45 ℃.Temperature of charge: 80 ℃, peristaltic pump rotating speed: 100r/min, gained granule are trifoliate orange art granule.
(7) fill:, carry out fill, promptly with the gained granule
Embodiment 4
Get 40 parts of Rhizoma Atractylodis Macrocephalae (parched)s, 20 parts of Fructus Aurantii Immaturus (parched), 6 parts on Folium Nelumbinis, adopt the following steps preparation:
(1) pulverize: Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) are ground into 60 purpose fine powders, standby.
(2) CO
2Supercritical extraction: get Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) fine powder in extraction kettle, heating extraction kettle and extraction-container reach predetermined temperature, send into the CO of certain flow rate
2Gas begins cycling extraction after regulating each still pressure, and wherein the extraction kettle temperature is 46 ℃, and pressure is 32Mpa, CO
2Flow velocity is 26L/h, and the extraction time is 1.5 hours.
(3) water is carried: CO learns from else's experience
2Rhizoma Atractylodis Macrocephalae (parched) that supercritical extraction is crossed and Fructus Aurantii Immaturus (parched) medicinal residues, Folium Nelumbinis medical material add 9 times of water gagings and decoct 2 times, and each 1 hour, filter, merging filtrate gets the water extract.
(4) membrance separation: after the water extract adopts the aperture to be the inorganic ceramic membrane filtration in 0.2 μ m aperture earlier, the inorganic ceramic membrane filtration in filtrate reuse 0.01 μ m aperture.It is 1.12 clear paste that permeate is evaporated to 60 ℃ of relative densities, standby.
(5) extract enclose: the beta-schardinger dextrin-of getting 10 times of amounts of extract weight, the water that adds 3 times of amounts of beta-schardinger dextrin-weight grinds well, pour in the colloid mill, slowly drip Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract with dissolve with ethanol continuously, pure consumption is 30% of an extract volume, mills 35 minutes, incline to, cold preservation was left standstill 30 hours, in 40 ℃ of vacuum dryings, promptly got the extract clathrate.
(6) granulate: extract clathrate and an amount of dextrin, stevioside mix, and put in the boiling spray granulation device, and clear paste is sprayed into.One time inlet temperature is 75 ℃; The secondary air temperature is 95 ℃; Leaving air temp is 55 ℃.Temperature of charge: 80 ℃, peristaltic pump rotating speed: 100r/min, gained granule are trifoliate orange art granule.
(7) fill:, carry out fill, promptly with the gained granule
Embodiment 5
Get 40 parts of Rhizoma Atractylodis Macrocephalae (parched)s, 20 parts of Fructus Aurantii Immaturus (parched), 6 parts on Folium Nelumbinis, adopt the following steps preparation:
(1) pulverize: Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) are ground into 20 purpose coarse powder, standby.
(2) CO
2Supercritical extraction: get Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) fine powder in extraction kettle, heating extraction kettle and extraction-container reach predetermined temperature, send into the CO of certain flow rate
2Gas begins cycling extraction after regulating each still pressure, and wherein the extraction kettle temperature is 52 ℃, and pressure is 32Mpa, CO
2Flow velocity is 26L/h, and the extraction time is 2.5 hours.
(3) water is carried: CO learns from else's experience
2Rhizoma Atractylodis Macrocephalae (parched) that supercritical extraction is crossed and Fructus Aurantii Immaturus (parched) medicinal residues, Folium Nelumbinis medical material add 7 times of water gagings and decoct 1 time, and each 2 hours, filter, merging filtrate gets the water extract.
(4) membrance separation: after the water extract adopts the aperture to be the inorganic ceramic membrane filtration in 0.2 μ m aperture earlier, the inorganic ceramic membrane filtration in filtrate reuse 0.01 μ m aperture.It is 1.18 clear paste that permeate is evaporated to 60 ℃ of relative densities, standby.
(5) extract enclose: the beta-schardinger dextrin-of getting 9 times of amounts of extract weight, the water that adds 2.5 times of amounts of beta-schardinger dextrin-weight grinds well, pour in the colloid mill, slowly drip Rhizoma Atractylodis Macrocephalae (parched) and Fructus Aurantii Immaturus (parched) supercritical extract with dissolve with ethanol continuously, pure consumption is 40% of an extract volume, mills 55 minutes, incline to, cold preservation was left standstill 30 hours, in 40 ℃ of vacuum dryings, promptly got the extract clathrate.
(6) granulate: extract clathrate and an amount of dextrin, stevioside mix, and put in the boiling spray granulation device, and clear paste is sprayed into.One time inlet temperature is 85 ℃; The secondary air temperature is 105 ℃; Leaving air temp is 42 ℃.Temperature of charge: 70 ℃, peristaltic pump rotating speed: 90r/min, gained granule are trifoliate orange art granule.
(7) fill:, carry out fill, promptly with the gained granule
Claims (3)
1, the particulate preparation technology of a kind of trifoliate orange art, the weight portion of selecting raw medicinal material for use is 40 parts of Rhizoma Atractylodis Macrocephalae (parched)s, 20 parts of Fructus Aurantii Immaturus (parched), 6 parts on Folium Nelumbinis is characterized in that this technology may further comprise the steps:
A, weighting raw materials Rhizoma Atractylodis Macrocephalae (parched) by weight ratio, Fructus Aurantii Immaturus (parched), Folium Nelumbinis, standby;
B, pulverizing: Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) are pulverized, mix homogeneously, standby;
C, supercritical extraction: get Rhizoma Atractylodis Macrocephalae (parched), Fructus Aurantii Immaturus (parched) hybrid particles in extraction kettle, CO
2Supercritical extraction, extracting pressure are 30-36Mpa, and the extraction kettle temperature is 40-60 ℃, CO
2Flow velocity is 24～30L/h, and the extraction time is 0.5-2.5 hour, collects extract, and is standby;
D, water are carried: CO learns from else's experience
2Rhizoma Atractylodis Macrocephalae (parched) that supercritical extraction is crossed and Fructus Aurantii Immaturus (parched) medicinal residues, Folium Nelumbinis add 6～10 times of water gagings and decoct 1～3 time, and each 1～3 hour, filter, merging filtrate gets the water extract;
E, membrance separation: after the water extract adopts the aperture to be the membrane filtration in 0.2 μ m aperture earlier, the membrane filtration in filtrate reuse 0.01 μ m aperture; The clear paste that it is 1.10-1.20 that permeate is evaporated to 60 ℃ of relative densities, standby;
F, extract enclose: get the beta-schardinger dextrin-that the 6-10 of extract weight doubly measures, the water that the 2-4 of adding beta-schardinger dextrin-amount doubly measures grinds well, pour in the colloid mill, slowly drip the extract with dissolve with ethanol continuously, pure consumption is the 15%-45% of extract volume, milled enclose 30-50 minute, inclining, and cold preservation was left standstill 12～48 hours, filters, in 40 ℃ of vacuum dryings, promptly get the extract clathrate;
G, granulation: extract clathrate and an amount of dextrin, stevioside mix, and put in the pellet fabrication device, and clear paste is sprayed into, and one time inlet temperature is 70-90 ℃; The secondary air temperature is 90-110 ℃; Leaving air temp is 40-50 ℃, and temperature of charge: 50-80 ℃, peristaltic pump rotating speed: 60-120r/min, gained granule are trifoliate orange art granule.
2, preparation technology according to claim 1 is characterized in that the film that adopts among the step e is an inorganic ceramic film.
3, preparation technology according to claim 1 is characterized in that Rhizoma Atractylodis Macrocephalae (parched) is the Rhizoma Atractylodis Macrocephalae behind the parched with bran, and Fructus Aurantii Immaturus (parched) is the Fructus Aurantii Immaturus behind the parched with bran.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579576A (en) * | 2012-02-27 | 2012-07-18 | 贵州威门药业股份有限公司 | Preparation methods of Chuanxiongchatiao granule extracts and preparations thereof |
| CN104161859A (en) * | 2014-05-29 | 2014-11-26 | 南京中山制药有限公司 | Traditional Chinese medicine composition for treating spleen and stomach diseases, and preparation method thereof |
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| CN102579576A (en) * | 2012-02-27 | 2012-07-18 | 贵州威门药业股份有限公司 | Preparation methods of Chuanxiongchatiao granule extracts and preparations thereof |
| CN104161859A (en) * | 2014-05-29 | 2014-11-26 | 南京中山制药有限公司 | Traditional Chinese medicine composition for treating spleen and stomach diseases, and preparation method thereof |
| CN104257818A (en) * | 2014-09-17 | 2015-01-07 | 中国中医科学院中医基础理论研究所 | Composition containing immature bitter orange extract and bighead atractylodes rhizome extract and application of composition |
| CN106938012A (en) * | 2017-05-15 | 2017-07-11 | 广州白云山敬修堂药业股份有限公司 | A kind of medicine of hair growth and preparation method thereof |
| CN106938012B (en) * | 2017-05-15 | 2020-02-11 | 广州白云山敬修堂药业股份有限公司 | Medicine for treating alopecia and preparation method thereof |
| CN110664960A (en) * | 2018-12-29 | 2020-01-10 | 南京中山制药有限公司 | Traditional Chinese medicine composition for gastric mucosa precancerous lesion and preparation method and application thereof |
| CN110721289A (en) * | 2018-12-29 | 2020-01-24 | 南京中山制药有限公司 | Preparation method of Renzhu stomach-invigorating granules |
| CN110664960B (en) * | 2018-12-29 | 2022-03-08 | 南京中山制药有限公司 | Traditional Chinese medicine composition for gastric mucosa precancerous lesion and preparation method and application thereof |
| CN114847414A (en) * | 2021-02-04 | 2022-08-05 | 山西中医药大学 | Functional traditional Chinese medicine fish bait for promoting gastrointestinal health of fishes |
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