Background technology
Superfine communication technique is the new technique developing rapidly in recent years.Effective ingredient in Chinese crude drug is distributed in cell mostly, and conventional decoction pieces can only make part effective ingredient discharge while decoction, utilization rate of active components 10-30%; And employing wall breaking pulverization technology; as the prepared slices of Chinese crude drugs being crushed to 300 order left and right; cell wall breaking rate will reach 86.7%; improve the stripping of effective ingredient in medical material; greatly strengthen its drug effect; utilization rate of active components, more than 90%, reaches and reduces medical material use amount and protection herb resource, also can improve the mass penalty drug effect of medicine simultaneously.But current main superfine powder technology still rests on the stage that traditional Chinese medicine powder is broken to ultra-fine powder.Because micropowder granulocyte sporoderm-broken rate increases, exist breaking cellular wall powder surface area to increase, out-of-shape, mobility, bad dispersibility, be easy to moisture absorption, the inherent characteristicses such as poor stability, by its granulation, the stability that improves product, preparation prepared by the present invention has well solved the problem of above existence, reaches the utilization of medical material and use to maximize.
At present, for there being following technical barrier in breaking cellular wall preparation and pelletization thereof: (1), although the utilization rate of current breaking cellular wall preparation Chinese medicine ingredients is high, breaking cellular wall powder body is easy to oxidized, and stability is not high, and drug effect is easily lost; (2) product that existing herbal species obtains by soft material granulation is difficult to ensure yield, disintegrative and stability simultaneously; (3) some herbal species is not suitable for adopting breaking cellular wall powder body-soft material granulation method to make preparation, as Fructus Lycii, Radix Achyranthis Bidentatae and so on; And the present invention is by the groping of great many of experiments, and the herbal species of suitable breaking cellular wall powder body-soft material granulation method is screened, and find out the condition of each step.
Rhizoma Polygoni Cuspidati, Bie Ming ?, tiger cane, bitter volt, sour cane, speckle cane, bitter cane root, Du's Radix Achyranthis Bidentatae, sour bar, speckle root, Rhizoma Dioscoreae Bulbiferae, Chinese sealavender root, horn grass, megalosaurus purple, speckle village root, DAJIEGU, acid bucket reed, an acid bar etc.For dry rhizome and the root of polygonaceae plant Rhizoma Polygoni Cuspidati Polygonum cuspidatum Sieb .et Zucc., there is the effects such as dampness removing jaundice eliminating, heat-clearing and toxic substances removing, eliminating stasis to stop pain, relieving cough and resolving phlegm, its effective ingredient is mainly dissociated anthraquinone and anthraquinone glycoside, mainly contain emodin, polygonin, to warm relative with illumination responsive, poor heat stability.Therefore,, if adopt traditional decocting method, easily destroy its effective ingredient or cause the loss of effective ingredient.Rhizoma Polygoni Cuspidati is prepared into Rhizoma Polygoni Cuspidati superfine powder, is conducive to improve the utilization rate of effective ingredient, but simultaneously due to the increase of powder specific-surface area detection, produce and be easy to the moisture absorption, oxidation, rotten etc. shortcoming.Therefore, on the basis that is prepared into superfine powder, also need its transformation for further processing, effectively to overcome these unfavorable factors, the therapeutic effect of maximized performance medicine.
Summary of the invention
Technical problem to be solved by this invention is, in order to overcome Rhizoma Polygoni Cuspidati breaking cellular wall powder body above shortcomings, to provide a kind of Rhizoma Polygoni Cuspidati breaking cellular wall preparation.
Above-mentioned technical problem to be solved by this invention is achieved by the following technical programs:
A kind of Rhizoma Polygoni Cuspidati breaking cellular wall preparation provided by the invention, adopt following technical scheme: Rhizoma Polygoni Cuspidati is carried out to wall breaking pulverization and obtain superfine powder, add ethanol-water solution fully to mix, make soft material, further extruding obtains wet grain again, the dry Rhizoma Polygoni Cuspidati breaking cellular wall preparation that obtains, the sporoderm-broken rate of described superfine powder is 80 ~ 95%; In described superfine powder 90% or above grain diameter be less than or equal to 39 μ m.
Rhizoma Polygoni Cuspidati breaking cellular wall preparation prepared by the present invention, can make consumer in the time taking without decoction, by can make with warm boiled water effective ingredient utilization maximize.
Rhizoma Polygoni Cuspidati first can be crushed to 100 orders, more further carry out superfine powder, make in superfine powder 90% or the grain diameter of above (such as being 90%, 91%, 92%, 93%, 94% or 95%) be less than or equal to 39 μ m.The superfine powder adopting in the present invention program, 90% grain diameter is preferably the powder body of 39 μ m, taking 35-39 μ m as many (such as can as 35,36,37,38 or 39 μ m).But what those skilled in the art can know understanding is that these embodiment can not be served as restriction of the present invention, as long as particle diameter is less than or equal to 39 μ m and all can realizes the present invention.
The present invention adopts ethanol-water solution to carry out wet granulation, and its outstanding advantage is without any need for other additives, can make superfine powder of the present invention by follow-up granulation, dry, becomes Rhizoma Polygoni Cuspidati preparation granules.But in this process, should adopt the ethanol-water solution of which kind of concentration, and proportioning between this solution and superfine powder, all to need the strict parameter of controlling, to make the characteristic applicable to Rhizoma Polygoni Cuspidati superfine powder such as humidity, solid content, viscosity of soft material, making between superfine powder to have effective adhesive; Further by the setting of specific squeezing parameter, soft material extruding is become to density, sizeable Rhizoma Polygoni Cuspidati granular preparation, makes its density/loft suitable, thus dry become finished product after, even if be positioned in air at room temperature, also can prevent the Oxidation of air.And, the finished product obtaining, in the time using warm boiled water, ultra-fine powder can comparatively promptly scatter, and makes effective ingredient dissolve rapidly and fully and spread, and improves utilization rate of active components.
The present invention, by repeatedly groping, has finally chosen following scheme:
When wet granulation, in the ethanol-water solution adopting, the mass fraction of ethanol is 35% ~ 90%; Preferably, the mass fraction of ethanol is 40 ﹪~80 ﹪, is more preferably 45 ﹪~75 ﹪.In the time that ethanol mass fraction is 35% ~ 45%, superfine powder is 1 ︰ 0.4 ~ 0.45 with ethanol-water solution than by weight, is preferably 1 ︰ 0.4; In the time that ethanol mass fraction is 46% ~ 55%, superfine powder is 1 ︰ 0.4 ~ 0.6 with ethanol-water solution than by weight, is preferably 1 ︰ 0.5 ~ 0.6; In the time that ethanol mass fraction is 56% ~ 65%, superfine powder is 1 ︰ 0.4 ~ 0.7 with ethanol-water solution than by weight, is preferably 1 ︰ 0.5 ~ 0.7; In the time that ethanol mass fraction is 66% ~ 75%, superfine powder is 1 ︰ 0.4 ~ 0.8 with ethanol-water solution than by weight, is preferably 1 ︰ 0.6 ~ 0.8, most preferably is 0.7 ~ 0.8; In the time that ethanol mass fraction is 76% ~ 90%, superfine powder is 1 ︰ 0.4 ~ 1.1 with ethanol-water solution than by weight, is preferably 1 ︰ 0.7 ~ 1.1, most preferably is 1 ︰ 0.8 ~ 1.0.
In the time that soft material extruding is become to wet grain, be preferably controlled at following condition: adopt prepackage 10 order~30 eye mesh screens, extruding dynamics 0.05Mpa~1Mpa, rotating speed 50r/min~100r/min; Preferably, extruding dynamics 0.4Mpa~0.6Mpa, rotating speed 75r/min~85r/min.
The wet grain particle diameter of extruding gained is 14 order ~ 30 orders, and when dry, baking temperature is 45 DEG C ~ 75 DEG C, and be 0.5h ~ 2.5h drying time.
The bulk density of the Rhizoma Polygoni Cuspidati breaking cellular wall preparation obtaining is 0.27g/ml~0.65g/ml.
Compared with prior art, the present invention has following beneficial effect:
(1) the Rhizoma Polygoni Cuspidati preparation obtaining by method of the present invention, its utilization rate of active components improves greatly, and utilization rate is close to 100%;
(2) the present invention is by groping to obtain suitable wet granulation technology, make pelletization except the adding of alcohol-water, do not introduce other any additives, can obtain the soft material of solid content, modest viscosity, successfully to push granulating technique, the Chinese medicinal granule stability forming is strong, is difficult for collapsing rotten in storage and transportation;
(3) extruding condition of the present invention has been groped suitable rotating speed and extruding force, makes thus stickiness, Rhizoma Polygoni Cuspidati granular preparation that density is moderate, obtain finished product stability strong in, take in process and make again its easy disintegrate disperse, be convenient to warm boiled water;
(4) compare with the Rhizoma Polygoni Cuspidati prepared slices of Chinese crude drugs with Rhizoma Polygoni Cuspidati micropowder, the data that are documented in table 2 and table 3 by embodiment 15 can find out, the moisture in Rhizoma Polygoni Cuspidati breaking cellular wall preparation of the present invention obviously reduces, and stability and the dissolution rate of effective ingredient improve greatly.
Detailed description of the invention
In order more clearly to understand technology contents of the present invention, describe in detail especially exemplified by following examples, but embodiments of the present invention are not limited to this.
Embodiment 1
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 39 μ m, add ethanol-water solution (ethanol mass fraction is 30%) wet method soft material processed, solution and superfine powder addition are than 0.4 ︰ 1(by weight), after mixing, through pre-installing 10 mesh sieves, select extruding rotating speed 50r/min, extruding dynamics 1MPa wet granular processed, in wet granular transposition heated-air circulation oven, sets 75 DEG C of baking temperatures, dry 2.5h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 2
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 39 μ m, add ethanol-water solution (ethanol mass fraction is 40%) wet method soft material processed, solution and superfine powder addition are than 0.5 ︰ 1(by weight), after mixing, through pre-installing 10 mesh sieves, select extruding rotating speed 60r/min, extruding dynamics 0.9MPa wet granular processed, in wet granular transposition vacuum microwave drying case, sets 45 DEG C of baking temperatures, dry 0.75h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 3
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 39 μ m, add ethanol-water solution (ethanol mass fraction is 50%) wet method soft material processed, solution and superfine powder addition are than 0.6 ︰ 1(by weight), after mixing, through pre-installing 20 mesh sieves, select extruding rotating speed 80r/min, extruding dynamics 0.7MPa wet granular processed, in wet granular transposition heated-air circulation oven, sets 75 DEG C of baking temperatures, dry 2.5h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 4
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (ethanol mass fraction is 60%) wet method soft material processed, solution and superfine powder addition are than 0.7 ︰ 1(by weight), after mixing, through pre-installing 30 mesh sieves, select extruding rotating speed 60r/min, extruding dynamics 0.5MPa wet granular processed, in wet granular transposition vacuum microwave drying case, sets 50 DEG C of baking temperatures, dry 0.5h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 5
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be ground in superfine powder through micronizing the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (second mass fraction is 65%) wet method soft material processed, solution and superfine powder addition are than 0.7 ︰ 1(by weight), after mixing, through pre-installing 20 mesh sieves, select extruding rotating speed 100r/min, extruding dynamics 0.05MPa wet granular processed, in wet granular transposition heated-air circulation air box, sets 70 DEG C of baking temperatures, dry 2.0h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 6
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be ground in superfine powder through micronizing the powder body that 90% grain diameter is less than or equal to 45 μ m, the solution wet method soft material processed that the mass fraction that adds ethanol-water solution is 70%, solution and superfine powder addition are than 0.8 ︰ 1(by weight), after mixing, through pre-installing 14 mesh sieves, select extruding rotating speed 70r/min, extruding dynamics 0.2MPa wet granular processed, adopts airpillow-dry, sets 85 DEG C of dry inlet temperature, dry 1.0h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 7
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be ground in superfine powder through micronizing the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (second mass fraction is 75%) wet method soft material processed, solution and superfine powder addition are than 0.8 ︰ 1(by weight), after mixing, through pre-installing 20 mesh sieves, select extruding rotating speed 75r/min, extruding dynamics 0.3MPa wet granular processed, in wet granular transposition heated-air circulation air box, sets 70 DEG C of baking temperatures, dry 2.0h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 8
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be ground in superfine powder through micronizing the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (second mass fraction is 80%) wet method soft material processed, solution and superfine powder addition are than 0.9 ︰ 1(by weight), after mixing, through pre-installing 30 mesh sieves, select extruding rotating speed 85r/min, extruding dynamics 0.4MPa wet granular processed, in wet granular transposition heated-air circulation air box, sets 70 DEG C of baking temperatures, dry 2.0h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 9
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (ethanol mass fraction is 90%) wet method soft material processed, solution and superfine powder addition are than 1.0 ︰ 1(by weight), after mixing, through pre-installing 30 mesh sieves, select extruding rotating speed 50r/min, extruding dynamics 1MPa wet granular processed, in wet granular transposition vacuum microwave drying case, sets 45 DEG C of baking temperatures, dry 0.75h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 10
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (ethanol mass fraction is 90%) wet method soft material processed, solution and superfine powder addition are than 1.1 ︰ 1(by weight), after mixing, through pre-installing 30 mesh sieves, select extruding rotating speed 60r/min, extruding dynamics 0.5MPa wet granular processed, in wet granular transposition vacuum microwave drying case, sets 50 DEG C of baking temperatures, dry 0.5h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 11
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (ethanol mass fraction is 65%) wet method soft material processed, solution and superfine powder addition are than 0.8 ︰ 1(by weight), after mixing, through pre-installing 30 mesh sieves, select extruding rotating speed 80r/min, extruding dynamics 0.3MPa wet granular processed, in wet granular transposition heated-air circulation oven, sets 70 DEG C of baking temperatures, dry 2.5h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 12
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be ground in superfine powder through micronizing the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (second mass fraction is 60%) wet method soft material processed, solution and superfine powder addition are than 0.8 ︰ 1(by weight), after mixing, through pre-installing 20 mesh sieves, select extruding rotating speed 80r/min, extruding dynamics 0.6MPa wet granular processed, in wet granular transposition heated-air circulation air box, sets 70 DEG C of baking temperatures, dry 2.0h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 13
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (ethanol mass fraction is 75%) wet method soft material processed, solution and superfine powder addition are than 0.8 ︰ 1(by weight), after mixing, through pre-installing 30 mesh sieves, select extruding rotating speed 45r/min, extruding dynamics 0.04MPa wet granular processed, in wet granular transposition vacuum microwave drying case, sets 50 DEG C of baking temperatures, dry 0.5h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 14
Get the clean medical material of Rhizoma Polygoni Cuspidati, after the coarse powder of coarse pulverization to 100 order left and right, be broken in superfine powder through superfine powder the powder body that 90% grain diameter is less than or equal to 45 μ m, add ethanol-water solution (ethanol mass fraction is 70%) wet method soft material processed, solution and superfine powder addition are than 0.8 ︰ 1(by weight), after mixing, through pre-installing 20 mesh sieves, select extruding rotating speed 105r/min, extruding dynamics 1.1MPa wet granular processed, in wet granular transposition heated-air circulation oven, sets 70 DEG C of baking temperatures, dry 2.5h, to dry, obtains Rhizoma Polygoni Cuspidati breaking cellular wall preparation after granulate screening.
Remarks: full marks are in 10.
Embodiment 15
Get 1 ~ 10 lower finished product of embodiment by end product quality standard test, result all meets regulation requirement under the relevant dosage form item of Chinese Pharmacopoeia, and result is as shown in table 1.
The quality standard assay of the each embodiment of table 1.
Further by 1 ~ 10 lower Rhizoma Polygoni Cuspidati breaking cellular wall preparation of embodiment and Rhizoma Polygoni Cuspidati superfine powder, the conventional decoction pieces of Rhizoma Polygoni Cuspidati, using character, moisture and polygonin as evaluation index, three is placed on 40 DEG C ± 2 DEG C of temperature after all adopting sealed plastic bag encapsulation, places each preparation stability of post-evaluation in 3 months under the condition of relative humidity 75% ± 5%.Result is as shown in table 2 below:
The accelerated stability comparing result of the each sample of table 2.
Dissolution is the important indicator of evaluating drug bioavailability, a step is by above accelerated stability test sample again: embodiment 4 samples, Rhizoma Polygoni Cuspidati micropowder sample and Polygonum Cuspidatum three, according to 2010 version " Chinese Pharmacopoeia " (two) annex XC " dissolution method " lower second " an oar method " test.Get simulated gastric fluid 1000ml, keep 37 DEG C ± 0.5 DEG C of temperature, rotating speed 90r/min, each sample thief 5g, add in simulated gastric fluid, respectively at 10,20,30,40,50,60,90, when 120min, each sampling 5ml(supplies sampling amount simultaneously) measure polygonin amount, shown in result table 3.
The Dissolution Rate Testing result of the each sample of table 3.
As can be seen from Table 3, in Rhizoma Polygoni Cuspidati breaking cellular wall preparation of the present invention, the dissolution rate of polygonin, far away higher than the dissolution rate of the polygonin in Rhizoma Polygoni Cuspidati micropowder and Polygonum Cuspidatum, has overcome Rhizoma Polygoni Cuspidati micropowder in prior art and has made the deficiency that dissolution rate declines after preparation.