CN102430029B - A kind of nano microcapsule for six ingredients with rehmannia and preparation technology thereof - Google Patents

A kind of nano microcapsule for six ingredients with rehmannia and preparation technology thereof Download PDF

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CN102430029B
CN102430029B CN201110381711.4A CN201110381711A CN102430029B CN 102430029 B CN102430029 B CN 102430029B CN 201110381711 A CN201110381711 A CN 201110381711A CN 102430029 B CN102430029 B CN 102430029B
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grams
nano
ingredients
rehmannia
microcapsule
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CN102430029A (en
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王卫国
赵永亮
侯启昌
崔羽佳
李鹏
古亚楠
孟甜甜
张鹏
丁金聚
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Henan University of Technology
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Henan University of Technology
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Abstract

The invention discloses a kind of nano microcapsule for six ingredients with rehmannia and preparation technology thereof, is based on traditional LIUWEI DIHUANG WAN formula, and Radix Rehmanniae Preparata, Poria, Rhizoma Alismatis are adopted multistage Dynamic Thermal circumfluence method to extract and concentrated; Fructus Corni, Cortex Moutan, Rhizoma Dioscoreae are carried out nanoscale pulverizing; By nanometer fine powder and concentrated solution Homogeneous phase mixing by a certain percentage, after carrying out freezing or spray drying treatment, make nano-microcapsule agent, finally, adopt corresponding preparation technique to make the dosage form be suitable for clinically.This technique has simple to operate, and technological process is short, parameter is easily controlled, with low cost, produce the advantage such as toxic and side effects without organic reagent.This nano microcapsule for six ingredients with rehmannia both can directly use, and also can be used as pharmaceutical intermediate.Obviously drug effect be can extend, medicining times and dosage reduced, the toxic and side effects reducing or eliminate traditional routine administration and produce.The products such as this product is more than 3 times of six drugs containing rehmanniae series products cycles of concentration on existing market, the comparable traditional concentrated pill of six ingredients with rehmannia of total consumption per day reduce 3-6 doubly.

Description

A kind of nano microcapsule for six ingredients with rehmannia and preparation technology thereof
Technical field
The present invention relates to a kind of nano microcapsule for six ingredients with rehmannia and preparation technology thereof, belong to Chinese medicine dosage form preparing technical field.
Background technology
Six drugs containing rehmanniae is made up of Radix Rehmanniae Preparata, Fructus Corni, Rhizoma Dioscoreae, Rhizoma Alismatis, Cortex Moutan, Poria Six-element Chinese medicine.Containing various active compositions such as polysaccharide, glycoside, terpenoid in Six-element medical material, research shows: in six drugs containing rehmanniae, acidic polysaccharose CA4-3 can directly act on B cell, improves immunity of organisms.In Fructus Corni, polysaccharide PFCAIII effectively can suppress vegetable oil being oxygenized, has effect of scavenging radical.In Fructus Corni, terpenoid ursolic acid has blood fat reducing, effect of lowering blood sugar.Easing pain and diminishing inflammation after paeonol in Cortex Moutan has been widely used in fracture operation, the aspect such as promote knitting and anxiolytic drugs to prepare, toxic and side effects is little compared with Conventional analgesics class medicine, and after treatment, mitigation is lasting.Six drugs containing rehmanniae is used for the symptoms such as enriching yin and nourishing kidney, dizziness and tinnitus, soreness of the waist and knees, night sweat seminal emission, there is anticancer, raising human immunity, anti-aging effects, be widely used in clinically treating tens of kinds of diseases, as hypertension, diabetes, chronic nephritis, climacteric syndrome, old-slow-bronchial tube and chemotherapy of tumors etc.
The former side of six drugs containing rehmanniae is used as medicine with the former powder of medical material, and dose is large, very inconvenience.For concentrated, refine medicine effective ingredient, now have the dosage forms such as six drugs containing rehmanniae concentrated pill, Liuweidihuang Oral Liquid, LIUWEIDIHUANG JIAONANG, Liuwei Dihuang granule and come out.The main pros and cons of existing conventional six drugs containing rehmanniae preparation technology are as follows: 1, full powder is used as medicine: the honeyed pill that the LIUWEI DIHUANG WAN method for making recorded as pharmacopeia and some pharmaceutical factory produce and the watered pill are all that Chinese medicine is helped powder through Ordinary pulverization, then make preparation.This preparation is that patient all can take down medicine on the surface, does not lose any composition.But it is too large that its drawback one is dose; Two is adopt the conventional cell wall pulverizing very difficult broken vegetable drug, and active component is difficult to release and is absorbed by the body.2, decocting technique: as Liuweidihuang Oral Liquid and concentrated pill etc.The all the components of Chinese medicine is all included in extractum on the surface, no longer worries cell wall breaking problem.But decoct for a long time, concentrated, repeatedly drying considerable active ingredient can be made to destroy and loss.As: in Fructus Corni, ursolic acid is alcohol dissolubility, water insoluble extract; Paeonol in Cortex Moutan more than 50 DEG C is easy to volatilize with water vapour.These two kinds important medicinal ingredients more also can not get.3, water extraction paeonol and alcohol extraction ursolic acid: as Liuweidihuang Oral Liquid and concentrated capsule, for retaining paeonol and ursolic acid, adopts decoction and alcohol sedimentation technique.Advantage significantly reduces dosage, and shortcoming is that precipitate with ethanol eliminates tannin, starch, protein, also eliminates the polysaccharide with important biomolecule activity.This method is to this kind of preparation of six drugs containing rehmanniae or take mixing polysaccharide as the preparation of effective ingredient be ill-considered, and complicated process of preparation, cost is higher.Certainly, due to the water-insoluble of ursolic acid, this technique also will make the yield of ursolic acid obviously reduce.4, macroporous resin adsorption technique: as LIUWEIDIHUANG JIAONANG, in order to meet, to represent component content up to standard, first obtains ursolic acid with ethanol to Fructus Corni backflow; Paeonol is obtained to Cortex Moutan distillation, and then by herbs ' water-decoctum through macroporous resin adsorption, makes preparation.But macroreticular resin absorbing method is not suitable for preparing polysaccharide, though medicine can concentrate the polysaccharide eliminating the effect of tool valuable pharmacological.
Summary of the invention
The object of the invention is to: overcome the defect that existing six drugs containing rehmanniae preparation technology exists, design a set of technical scheme and prepare a kind of nano microcapsule for six ingredients with rehmannia, while efficient reservation medical material effective ingredient, reach the object of desirable concentrated Chinese traditional compound medicine.Meanwhile, can also drug effect be extended, reduce medicining times and dosage, the toxic and side effects reducing or eliminate traditional routine administration and produce.The present invention adopts superfine communication technique by Fructus Corni, Cortex Moutan, Rhizoma Dioscoreae nanorize: the dissolution improving its effective ingredient first; Second make vegetable drug fiber particle increase, be beneficial to medicine disintegration stripping; Three losses avoiding high temperature and water extraction commute volatile active composition paeonol and Alcohol soluble composition ursolic acid; Four fundamental rules make the good anti-moisture absorption effect of starch in Rhizoma Dioscoreae, polysaccharide be given full play to and utilize.The present invention adopts multistage solvent circulation Dynamic Thermal technique of backflow to the less medical material Radix Rehmanniae Preparata of temperature impact, Rhizoma Alismatis, Poria, carry out extraction to concentrate, the water extracting liquid with certain viscosity just can be wrapped on nanometer fine powder, form nano-microcapsule after drying, reach the object to medicine concentrated, refine further.The present invention adopts lyophilization or spraying dry to replace traditional normal heating or forced air drying treatment technology, efficiently can intactly retain the important active ingredient such as polysaccharide, ursolic acid, paeonol.Preparation process does not add any adjuvant, and 100% crude drug source component can do the formulations such as further granulation, tabletting.
Nano microcapsule for six ingredients with rehmannia, its crude drug formula is Radix Rehmanniae Preparata 1408 grams, Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams.Radix Rehmanniae Preparata, Poria, Rhizoma Alismatis are added water and adopt the extraction of multistage solvent circulation Dynamic Thermal circumfluence method concentrated, concentrated solution filters and the rear cryopreservation of process of lowering the temperature is for subsequent use; Fructus Corni, Cortex Moutan, Rhizoma Dioscoreae are first carried out coarse pulverization, then carries out ultra micro or nanoscale pulverizing; Again by nanometer fine powder and concentrated solution Homogeneous phase mixing in proportion, after carrying out lyophilisation or spray drying treatment, and obtained nano microcapsule for six ingredients with rehmannia; Finally, then according to Clinical practice requirement, the dosage form be suitable for clinically is made.
The mean diameter of described nano-microcapsule is 500 ± 50nm.
The preparation technology of nano microcapsule for six ingredients with rehmannia comprises the following steps:
The first step, according to the physicochemical property of Six-element medical material and effect, is carried out classification to active ingredients of medicinal materials and is extracted concentrated preparation:
A. multistage solvent circulation Dynamic Thermal reflux, extract, concentration technology: Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, add water 10-100L, and multistage solvent circulation Dynamic Thermal reflux, extract, concentrates 1-4h.Concentration of liquid medicine to 5L-30L, medical filtration, for subsequent use;
B. micronizing technique: Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams first carry out routine and pulverize, and cross 80 mesh sieves, then carry out nanoscale pulverizing, nanoscale fine powder crosses 1250 orders with top sieve, for subsequent use; The suitableeest technological parameter of micronizing: speed of mainshaft 300r/min-450r/min, pulverizes 1-3h;
Second step mixes:
C. by the medicinal liquid after above-mentioned concentrating and nano powder Homogeneous phase mixing, to suspension or paste, for subsequent use;
The six drugs containing rehmanniae nano suspending liquid that 3rd step lyophilisation or spraying dry second step obtain or ointment;
4th step is carried out fragmentation process to dried sample as required or is not processed, overground sieve after, obtain nano microcapsule for six ingredients with rehmannia;
5th step, according to Clinical practice requirement, adopts corresponding preparation technique method to make the dosage form be suitable for clinically.
In above-mentioned preparation technology:
The multistage solvent circulation Dynamic Thermal reflux, extract, of preparation technology concentrates condition and is made up of the following factor:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, add extraction water 10L-100L, and put into Dynamic Thermal reflux, extract, device, T=90 DEG C-100 DEG C, reflux, extract, 1h 4h, extracting liquid filtering is concentrated into 5L-30L, for subsequent use.
The micronizing condition of preparation technology is made up of the following factor:
Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams first carry out routine and pulverize, and cross 80 mesh sieves, then carry out nanoscale pulverizing, the suitableeest technological parameter of micronizing: speed of mainshaft 300r/min-450r/min, pulverize 1-3h; Nanoscale fine powder crosses 1250 mesh sieves, nano powder mean diameter 250 ± 30nm, for subsequent use.
The mixing condition of preparation technology and ratio are made up of the following factor:
To extract concentrated medicinal liquid and nano powder Homogeneous phase mixing at normal temperatures, the suitableeest volume ratio of nano powder and concentrated medicament is: 1: 0.5--1: 20; To suspension or paste, for subsequent use.
The lyophilisation condition of preparation technology is for be made up of the following factor:
Nano suspending liquid or ointment-20 DEG C of pre-cooling 30min-24h will be prepared, put into frozen vacuum dryer and carry out drying, the suitableeest technological parameter: temperature-50 DEG C--40 DEG C, vacuum 7.90-120.0Pa, lyophilizing 6h-24h.
Carrying out spray-dired concrete technology condition to adopting the nano suspending liquid prepared by A → C technique is: inlet temperature 110 DEG C-160 DEG C, outlet temperature 50 DEG C-100 DEG C, power of fan 1.5kw, dry 2-10s.
This nano microcapsule for six ingredients with rehmannia, can directly apply as pharmaceutical intermediate; Or under the condition of not adding or adding adjuvant or auxiliary agent, directly granulate, tabletting, fills capsule or prepare oral liquid, make dosage form applicable clinically or directly use as powder.
Nano microcapsule for six ingredients with rehmannia directly can be taken as powder, every day only need take once, 0.9-1.8g/ time, the products such as this product is more than 3 times of six drugs containing rehmanniae series products cycles of concentration on existing market, the comparable traditional concentrated pill of six ingredients with rehmannia of total consumption per day reduce 3-6 doubly.This six drugs containing rehmanniae nano-microcapsule body, because having medicated powder good fluidity, stability is high, hydroscopicity is extremely low feature, also can be used as pharmaceutical intermediate and using: do not need to add any adjuvant, do not need drying repeatedly namely to can be made into tablet, capsule, granule or prepare oral liquid (oral liquid only need add the aseptic warm water of a certain amount of solvent or pure water stirs evenly).
The present invention prepares six drugs containing rehmanniae nano-microcapsule technical matters method and has simple to operate, and technological process is short, and parameter is easily controlled, with low cost, the feature such as impact that produces toxic and side effects without organic reagent, meets industrial mass production requirement.The nano microcapsule for six ingredients with rehmannia mean diameter made is 500 ± 50nm (see table 1), powder body θ angle of repose is minimum to be reached 31 ° (see table 2), the settling ratio 0.95 (see table 3) of 24h six drugs containing rehmanniae nano-microcapsule, paeonol dissolution exceeds 68.18% (see table 4) than traditional product water-honeyed pill, paeonol content exceeds 19.83% than the concentrated pill standard specified in pharmacopeia, and the concentrating degree of nano-microcapsule manufactured goods exceeds more than 3 times than the existing six drugs containing rehmanniae dosage form in market.In six drugs containing rehmanniae nano-microcapsule powder body, paeonol dissolution significantly increases, and powder body is dispersed, and good fluidity, stability are high, directly as powder, can also can be used as the intermediate of granule, Tablet and Capsula filling etc.
The microscopic features that table 1 routine pulverizes coarse powder and micronizing nano powder compare
Table 2 different dry drying method prepares the powder fluidity results contrast of nano microcapsule for six ingredients with rehmannia
Table 3 coarse powder/nano powder/nano-microcapsule agent stability result compares (settling ratio)
Table 4 paeonol accumulative dissolution compares
Nano microcapsule for six ingredients with rehmannia of the present invention and preparation technology thereof, compared with existing six drugs containing rehmanniae formulation technologies, have following marked feature:
1. Freeze Drying Technique replaces conventional drying techniques: the effumability composition paeonol in Cortex Moutan is able to efficient reservation, avoids repeatedly decocting in Conventional concentration ball, oral liquid, capsule, tablets and other formulations preparation process, concentrate, glycoside, terpenoid and paeonol content that drying causes lose.
2. superfine communication technique replaces the conventional omnipotent disintegrating process of tradition: (1) ultra micro or nanoscale are pulverized and made crude drug cell wall completely broken, and effective ingredient, can directly stripping because not affecting by solvent penetration pressure; (2), after nano-particle enters small intestinal, the time that the herb in granule form of refinement adsorbs on small bowel is longer, and effective ingredient is longer for release time; (3) six drugs containing rehmanniae raw material is vegetalitas Chinese crude drug, and medical material super-refinement makes fiber particle in vegetable drug greatly increase, and contributes to the disintegrate stripping of active ingredient after medical material enters small intestinal.
Conventional size reduction cannot make cell wall thoroughly broken, and active ingredient is difficult to release, and simultaneously thicker herb in granule form time of adsorbing on small bowel is shorter, and this is also the reason that Chinese medicine effective ingredient dissolution is low, bioavailability is poor.This nano microcapsule for six ingredients with rehmannia can significantly improve active ingredient dissolution and bioavailability.
The technology that lyophilisation or spraying dry combine with multistage solvent circulation Dynamic Thermal reflux, extract, effectively can be overcome the defect that existing six drugs containing rehmanniae preparation technology exists by the present invention, simultaneously, the present invention adopts superfine communication technique to replace conventional size reduction to prepare nano-microcapsule, the phenomenon that large, black, thick and absorption difference, effect are slow by for a change Chinese medicine, for the real modernization of Chinese medicine, internationalization contribute.
3. little medical material is affected on water extraction temperature and carries out circumfluence distillation process: can not only complete reservation polysaccharide and other effective ingredient, further medical material is concentrated simultaneously, refine.Make the medicine concentrating degree of this nano microcapsule for six ingredients with rehmannia higher than other six drugs containing rehmanniae series products dosage form existing.
4. this nano microcapsule for six ingredients with rehmannia is as the superiority of pharmaceutical intermediate: after Six-element medical material is made six drugs containing rehmanniae nano-microcapsule, powder body is dispersed, mobility, good stability, be no matter directly as powder, tabletting process, prepare capsule, or granulate, all there is feasibility.Radix Rehmanniae Preparata extracting solution viscosity is comparatively large, can directly as medicine adhesive.Containing much starch and polysaccharide in Rhizoma Dioscoreae, can replace amylum pregelatinisatum, also have good anti-moisture absorption simultaneously in tablet manufacture, the six drugs containing rehmanniae nano-microcapsule of lyophilisation places a month weightening finish < 1% in air.Do not add any adjuvant in preparation process, produce the features such as the impact of toxic and side effects without organic reagent.
5. this nano microcapsule for six ingredients with rehmannia obviously can extend drug effect, reduces medicining times and dosage, the toxic and side effects reducing or eliminate traditional routine administration and produce.The products such as directly can take as powder, every day only need take once, 0.9-1.8g/ time, and this product is more than 3 times of six drugs containing rehmanniae series products cycles of concentration on existing market, the comparable traditional concentrated pill of six ingredients with rehmannia of total consumption per day reduce 3-6 doubly.
Detailed description of the invention
Embodiment 1:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=90 DEG C-95 DEG C, reflux, extract, 3-4h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out ultra micro or nanoscale pulverizing, the speed of mainshaft is 300r/min-350r/min, after pulverizing 3h, crosses 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 0.5: 1 Homogeneous phase mixing, to paste, for subsequent use.After above-mentioned six drugs containing rehmanniae nano suspending liquid-20 DEG C of pre-cooling 30min, put into frozen vacuum dryer, condenser temperature-50 DEG C--40 DEG C, vacuum 90-120Pa, dry 6h-12h.Fragmentation process is carried out to dried sample, overground sieve after, obtain nano microcapsule for six ingredients with rehmannia.Respond well.
Embodiment 2:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 350r/min-400r/min, after pulverizing 2h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 1: 0.5 Homogeneous phase mixing, to suspension or paste, for subsequent use.After above-mentioned six drugs containing rehmanniae nano suspending liquid-20 DEG C of pre-cooling 24h, put into frozen vacuum dryer, condenser temperature-50 DEG C--40 DEG C, vacuum 7.90-30.20Pa, dry 20h-24h, carry out fragmentation process to dried sample, overground sieve after, obtain nano microcapsule for six ingredients with rehmannia.Best results.
Embodiment 3:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=98 DEG C-100 DEG C, reflux, extract, 1h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 400r/min-450r/min, after pulverizing 1h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 20: 1 Homogeneous phase mixing, to suspension, for subsequent use.After above-mentioned six drugs containing rehmanniae nano suspending liquid-20 DEG C of pre-cooling 4h, put into frozen vacuum dryer, condenser temperature-50 DEG C--40 DEG C, vacuum 60-80Pa, dry 6h-24h, carry out fragmentation process to dried sample, overground sieve after, obtain nano microcapsule for six ingredients with rehmannia.Respond well.
Embodiment 4:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=90 DEG C-95 DEG C, reflux, extract, 2-3h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 300r/min-350r/min, after pulverizing 3h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 10: 1 Homogeneous phase mixing, to suspension, for subsequent use.Above-mentioned six drugs containing rehmanniae nano suspending liquid is carried out spraying dry, and spray drying condition is: inlet temperature 130 DEG C-160 DEG C, outlet temperature 50 DEG C-100 DEG C, power of fan 1.5kw, dry 2-10s.Obtain nano microcapsule for six ingredients with rehmannia, respond well.
Embodiment 5:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 1-2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 300r/min-350r/min, after pulverizing 3h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 5: 1 Homogeneous phase mixing, to suspension, for subsequent use.Above-mentioned six drugs containing rehmanniae nano suspending liquid is carried out spraying dry, and spray drying condition is: inlet temperature 110 DEG C-130 DEG C, outlet temperature 50 DEG C-100 DEG C, power of fan 1.5kw, dry 2-10s.Obtain nano microcapsule for six ingredients with rehmannia, best results.
Embodiment 6:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 1-2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 300r/min-350r/min, after pulverizing 3h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 12: 1 Homogeneous phase mixing, to suspension, for subsequent use.Above-mentioned six drugs containing rehmanniae nano suspending liquid is carried out spraying dry, and spray drying condition is: inlet temperature 110 DEG C-130 DEG C, outlet temperature 50 DEG C-100 DEG C, power of fan 1.5kw, dry 5-10s.Granule is made again after obtaining six drugs containing rehmanniae nano-microcapsule, respond well.
Embodiment 7:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 1-2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 300r/min-350r/min, after pulverizing 3h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 3: 1 Homogeneous phase mixing, to suspension, for subsequent use.Above-mentioned six drugs containing rehmanniae nano suspending liquid is carried out spraying dry, and spray drying condition is: inlet temperature 110 DEG C-130 DEG C, outlet temperature 50 DEG C-100 DEG C, power of fan 1.5kw, dry 2-5s.Tablet is pressed into again, excellent effect after obtaining six drugs containing rehmanniae nano-microcapsule.
Embodiment 8:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 1-2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 300r/min-350r/min, after pulverizing 3h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 8: 1 Homogeneous phase mixing, to suspension, for subsequent use.Above-mentioned six drugs containing rehmanniae nano suspending liquid is carried out spraying dry, and spray drying condition is: inlet temperature 110 DEG C-130 DEG C, outlet temperature 50 DEG C-100 DEG C, power of fan 1.5kw, dry 3-6s.Refill after obtaining six drugs containing rehmanniae nano-microcapsule and make capsule into capsule, excellent effect.
Embodiment 9:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 350r/min-400r/min, after pulverizing 2h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 1: 0.5 Homogeneous phase mixing, to suspension or paste, for subsequent use.After above-mentioned six drugs containing rehmanniae nano suspending liquid-20 DEG C of pre-cooling 24h, put into frozen vacuum dryer, condenser temperature-50 DEG C--40 DEG C, vacuum 7.90-30.20Pa, dry 20h-24h, carries out fragmentation process to dried sample, overground sieve after, six drugs containing rehmanniae nano-microcapsule refills and makes capsule into capsule, best results.
Embodiment 10:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 350r/min-400r/min, after pulverizing 2h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 2: 0.5 Homogeneous phase mixing, to suspension or paste, for subsequent use.After above-mentioned six drugs containing rehmanniae nano suspending liquid-20 DEG C of pre-cooling 5h, put into frozen vacuum dryer, condenser temperature-50 DEG C--40 DEG C, vacuum 7.90-30.20Pa, dry 10h-15h, carries out fragmentation process to dried sample, overground sieve after, granule is made again after obtaining six drugs containing rehmanniae nano-microcapsule, respond well.
Embodiment 11:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 350r/min-400r/min, after pulverizing 2h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 18: 1 Homogeneous phase mixing, to suspension, for subsequent use.After above-mentioned six drugs containing rehmanniae nano suspending liquid-20 DEG C of pre-cooling 12h, put into frozen vacuum dryer, condenser temperature-50 DEG C--40 DEG C, vacuum 7.90-30.20Pa, dry 20h-24h, carries out fragmentation process to dried sample, overground sieve after, tablet is pressed into again, excellent effect after obtaining six drugs containing rehmanniae nano-microcapsule.
Embodiment 12:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, the 10L that adds water puts into circumfluence distillation concentrator, T=96 DEG C-98 DEG C, reflux, extract, 2h, and extracting liquid filtering is for subsequent use.Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams carry out routine and pulverize, and drop into super micron mill after crossing 80 mesh sieves and carry out nanoscale pulverizing, the speed of mainshaft is 350r/min-400r/min, after pulverizing 2h, cross 1250 orders with top sieve, for subsequent use.Above extracting solution and nanoscale fine powder are pressed 18: 1 Homogeneous phase mixing, to suspension, for subsequent use.After above-mentioned six drugs containing rehmanniae nano suspending liquid-20 DEG C of pre-cooling 12h, put into frozen vacuum dryer, condenser temperature-50 DEG C--40 DEG C, vacuum 7.90-30.20Pa, dry 20h-24h, carries out fragmentation process to dried sample, overground sieve after, add solvent in the ratio of 1-15-30 again after obtaining six drugs containing rehmanniae nano-microcapsule and make oral liquid, excellent effect.

Claims (9)

1. a nano microcapsule for six ingredients with rehmannia, it is characterized in that: its crude drug formula is Radix Rehmanniae Preparata 1408 grams, Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, be Radix Rehmanniae Preparata, Poria, Rhizoma Alismatis are added water and adopt the extraction of multistage solvent circulation Dynamic Thermal circumfluence method concentrated, concentrated solution filters and the rear cryopreservation of process of lowering the temperature is for subsequent use; Fructus Corni, Cortex Moutan, Rhizoma Dioscoreae are first carried out coarse pulverization, then carries out ultra micro or nanoscale pulverizing; Again by nanometer fine powder and concentrated solution Homogeneous phase mixing in proportion, after carrying out lyophilisation or spray drying treatment, and obtained nano microcapsule for six ingredients with rehmannia; Finally, the dosage form be suitable for clinically is made.
2. according to nano microcapsule for six ingredients with rehmannia according to claim 1, it is characterized in that: the mean diameter of described nano-microcapsule is 500 ± 50nm.
3. according to a preparation technology for nano microcapsule for six ingredients with rehmannia described in claim 1, it is characterized in that: this preparation technology comprises the following steps:
The first step, according to the physicochemical property of Six-element medical material and effect, is carried out classification to active ingredients of medicinal materials and is extracted concentrated preparation:
A. multistage solvent circulation Dynamic Thermal reflux, extract, concentration technology: Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, add water 10-100L, and Dynamic Thermal reflux, extract, concentrates 1-4h, and concentration of liquid medicine is filtered to 5L-30L, for subsequent use;
B. micronizing technique: Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams first carry out routine and pulverize, and cross 80 mesh sieves, then carry out ultra micro or nanoscale pulverizing, nanoscale fine powder crosses 1250 orders with top sieve, for subsequent use; The suitableeest technological parameter of micronizing: speed of mainshaft 300r/min-450r/min, pulverizes 1-3h;
Second step mixes:
C. by the medicinal liquid after above-mentioned concentrating and nano powder Homogeneous phase mixing, to suspension or paste, for subsequent use;
The six drugs containing rehmanniae nano suspending liquid that 3rd step lyophilisation or spraying dry second step obtain or ointment;
4th step is carried out fragmentation process to dried sample as required or is not processed, overground sieve after, obtain nano microcapsule for six ingredients with rehmannia;
5th step, according to Clinical practice requirement, adopts corresponding preparation technique method to make the dosage form be suitable for clinically.
4. according to nano microcapsule for six ingredients with rehmannia preparation technology according to claim 3, it is characterized in that: the multistage solvent circulation Dynamic Thermal reflux, extract, of preparation technology concentrates condition and is made up of the following factor:
Radix Rehmanniae Preparata 1408 grams, 528 grams, Poria, Rhizoma Alismatis 538 grams, add extraction water 10L-100L, puts into Dynamic Thermal reflux, extract, device, and T=90 ° of C-100 ° C, reflux, extract, 1h-4h, extracting liquid filtering is concentrated into 5L-30L, for subsequent use.
5. according to nano microcapsule for six ingredients with rehmannia preparation technology according to claim 3, it is characterized in that: the micronizing condition of preparation technology is made up of the following factor:
Fructus Corni 704 grams, Cortex Moutan 528 grams, Rhizoma Dioscoreae 704 grams first carry out routine and pulverize, and cross 80 mesh sieves, then carry out ultra micro or nanoscale pulverizing, and the suitableeest technological parameter of micronizing: speed of mainshaft 300r/min-450r/min, pulverizes 1-3h; Nanoscale fine powder crosses 1250 mesh sieves, nano powder mean diameter 250 ± 30nm, for subsequent use.
6. according to nano microcapsule for six ingredients with rehmannia preparation technology according to claim 3, it is characterized in that: the mixing condition of preparation technology and ratio are made up of the following factor:
To extract concentrated medicinal liquid and nano powder Homogeneous phase mixing at normal temperatures, the suitableeest volume ratio of nano powder and concentrated medicament is: 1:0.5---1:20; To suspension or paste, for subsequent use.
7. according to nano microcapsule for six ingredients with rehmannia preparation technology according to claim 3, it is characterized in that: the lyophilisation condition of preparation technology is for be made up of the following factor:
By the nano suspending liquid of preparation or ointment-20 ° of C pre-cooling 30min-24h, put into frozen vacuum dryer and carry out drying, the suitableeest technological parameter: temperature-50 ° of C--40 ° C, vacuum 7.90-120.0Pa, lyophilizing 6h-24h.
8. according to nano microcapsule for six ingredients with rehmannia preparation technology according to claim 3, it is characterized in that: carrying out spray-dired concrete technology condition to adopting the nano suspending liquid prepared by A → C technique is: inlet temperature 110 DEG C-160 DEG C, outlet temperature 50 DEG C-100 DEG C, power of fan 1.5kw, dry 2-10s.
9. a nano microcapsule for six ingredients with rehmannia as claimed in claim 1, can directly apply as pharmaceutical intermediate; Or under the condition of not adding or adding adjuvant or auxiliary agent, directly granulate, tabletting, fills capsule or prepare oral liquid, make dosage form applicable clinically or directly use as powder.
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微囊化技术在中药制剂中的应用;贾宁等;《南京中医药大学学报》;20081110;第24卷(第06期);431-432 *

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