CN103356796A - Blood stasis removing particles and preparation method thereof - Google Patents
Blood stasis removing particles and preparation method thereof Download PDFInfo
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Abstract
The invention discloses blood stasis removing particles and a preparation method thereof. The preparation method comprises the following steps of: taking 11 medicinal materials such as peach kernel, flowers carthami and Angelica sinensis in proportion according to a formula; adding 4-12 times of water to decoct for 0.5-2 hours; taking a filtrate; then, adding 2-10 times of water into the raw materials to decoct for 0.5-2 hours to filter; combining the filtrates twice; concentrating to 2-4 times of total weight of the raw material medicines; adding appropriate accessories; uniformly mixing; spraying and drying to obtain sprayed powder; and drying, pressing and prilling to obtain the particles. The particles disclosed by the invention have the advantages that the daily delivery dosage of the blood stasis removing particles can reach 76g which is consistent with that of a conventional decoction, wherein the retention rates of the effective components hydroxyl carthamin yellow A, paeoniflorin, naringin and ferulic acid are approximate to those of the decoction, so that the defect of marketed similar preparations, namely decoction patent medicines, is overcome.
Description
Technical field
The present invention relates to the Chinese drug preparation field, particularly relate to a kind of 'Xue Fu Zhu Yu ' granule and preparation method thereof.
Background technology
Decoction for removing blood stasis comes from the errors in Medicine Corrected of Qing Dynasty's Wang Qingren, and prescription consists of Semen Persicae 12g, Flos Carthami 9g, Radix Angelicae Sinensis 9g, Rhizoma Chuanxiong 5g, Radix Rehmanniae 9g, Radix Paeoniae Rubra 6g, Fructus Aurantii 6g, Radix Platycodonis 5g, Radix Achyranthis Bidentatae 9g, Radix Bupleuri 3g, Radix Glycyrrhizae 3g.This prescription has the effect of blood circulation promoting and blood stasis dispelling, promoting the circulation of QI to relieve pain.Be mainly used in clinically treating in the heart syndrome of blood stasis, chest pain, headache with the passing of time, aching as needle stabbing and the place of deciding is arranged, or singultus is with the passing of time more than, or interior-heat is unhappy, or palpitation and insomnia, being irritable and getting angry easily enters an act hectic fever, lip is dark or two orders are black dull, body of the tongue is dim red or ecchymosis, hesitant pulse or stringy and tense pulse arranged.Decoction for removing blood stasis is as treating the in the heart classics recipe of syndrome of blood stasis, being widely used clinically.
Under existing new drug development and preparation technology's pattern, to produce greatly the patent medicine preparation of gained and compare with former clinical decoction, the retention rate of effective ingredient and drug effect have had larger difference.The reason of this species diversity is: the technological process that decoction did not experience such as extract, concentrated, dry under the Industry Model; Limited the crude drug quantity not sufficient of the patent medicine preparation that causes by moulding process and oral dose.
Extraction under the Industry Model, concentrated, dry, moulding process route and parameter, the concentrated and dry run that especially clinical decoction did not experience easily makes index components in the medical material in large production, the particularly retention rate of unstability effective ingredient reduction.According to ancient prescription, taking the crude drug amount 'Xue Fu Zhu Yu ' decoction day will reach 76g and just can play preferably effect, through the decoction of routinely decoction technique decoction and the S-A Hydroxysafflor yellow A in the existing formulation of ' Xuefu Zhuyu Decoction, peoniflorin, the day dose of the effective ingredient such as naringin and ferulic acid compares, the result shows that the content of taking index components conventional decoction day is higher than the capsule that has gone on the market far away, the preparations such as oral liquid (see the following form 1,2), as seen with regard to taking index components and day the crude drug amount, the component content that existing preparation keeps does not reach the content of former decoction, greatly affects the effectiveness of medicine.
Table 1 'Xue Fu Zhu Yu ' listing formulation samples lot number and usage and dosage
| Title | Product batch number | Day dose | Specification |
| XUEFU ZHUYU JIAONANG | H03050 | 12/day | 0.4g/ grain |
| The 'Xue Fu Zhu Yu ' granule | 080104.029 | 3 bags/days | The 5g/ bag |
| XUEFU ZHUYU KOUFUYE | 0807006 | 3/day | 10ml/ props up |
Table 2 formulation of ' Xuefu Zhuyu Decoction index components is content and day dose in preparation unit
Summary of the invention
The object of the present invention is to provide a kind of day to take the crude drug amount consistent with clinical decoction, the 'Xue Fu Zhu Yu ' granule that effective ingredient retention rate and former side's decoction are approximate.
For achieving the above object, the present invention has taked following technical scheme:
A kind of preparation method of 'Xue Fu Zhu Yu ' granule, the crude drug of described 'Xue Fu Zhu Yu ' granule forms and weight ratio is: Semen Persicae 11-13 part; Flos Carthami 8-10 part; Radix Angelicae Sinensis 8-10 part; Radix Rehmanniae 8-10 part; Rhizoma Chuanxiong 4-6 part; Radix Paeoniae Rubra 5-7 part; Radix Achyranthis Bidentatae 8-10 part; Radix Platycodonis 4-6 part; Radix Bupleuri 2-4 part; Fructus Aurantii 5-7 part; Radix Glycyrrhizae 2-4 part may further comprise the steps:
(1) take by weighing in proportion the above-mentioned raw materials medicine, add the decocting that 4-12 doubly measures and boiled 0.5-2 hour, get filtrate, the decocting that adds again 2～10 times of amounts boils filtration in 0.5-2 hour, merges gained filtrate twice;
(2) filtrate that step (1) is obtained is reduced pressure under 50-80 ℃ the condition at-0.05Mpa, is concentrated into weight and is the 2-4 of crude drug gross weight doubly, gets extractum or concentrated solution;
(3) add adjuvant in the extractum that step (2) is obtained or the concentrated solution, described adjuvant is soluble starch or betacyclodextrin, and the 0-0.50 that described adjuvant addition is the crude drug gross weight times, spray drying gets spray powder;
(4) spray powder that step (3) is obtained is granulated, and get final product.
Among embodiment, described step takes by weighing the above-mentioned raw materials medicine in (1) in proportion therein, adds 10 times of water gagings and decocts 1 hour, gets filtrate, adds 8 times of water gagings again and decocts and filtered in 1 hour, merges gained filtrate twice.
Among embodiment, the technological parameter of filtrate decompression is 50-70 ℃ in the described step (2) therein.
Among embodiment, spray-dired temperature is intake air temperature 150-180 ℃ in the described step (3), 80-100 ℃ of air outlet temperature therein.
Among embodiment, spray-dired technological parameter is in the described step (3): 150 ℃ of intake air temperatures, 80 ℃ of air outlet temperature therein.
Among embodiment, spray powder is granulated through dry-pressing in the described step (4) therein, and the technological parameter that dry-pressing is granulated is that principal pressure is 3.5-4.5Mpa, and charging rate is 300-350rpm, and roll rotational speed is 50-80rpm.
Among embodiment, the technological parameter that dry-pressing is granulated in the described step (4) is that principal pressure is 4Mpa therein, and charging rate is 300rpm, and roll rotational speed is 50rpm.
On the other hand, the invention provides a kind of 'Xue Fu Zhu Yu ' granule according to above-mentioned preparation method gained.
Among embodiment, taking the crude drug amount day of this 'Xue Fu Zhu Yu ' granule is 76 grams therein.
Among embodiment, the crude drug of described 'Xue Fu Zhu Yu ' granule forms and weight ratio is: 12 parts in Semen Persicae therein; 9 parts on Flos Carthami; 9 parts of Radix Angelicae Sinensis; 9 parts of Radix Rehmanniae; 5 parts of Rhizoma Chuanxiongs; 6 parts of Radix Paeoniae Rubra; 9 parts of Radix Achyranthis Bidentataes; 5 parts of Radix Platycodoniss; 3 parts of Radix Bupleuri; 6 parts of Fructus Aurantiis; 3 parts in Radix Glycyrrhizae.
The present invention adopts extraction process by water according to the character of clinical application experience and prescription medical material effective ingredient; And according to giving solid yield in the experiment (about 40%) and taking crude drug amount (76g) every day, in conjunction with clinical application, determine that dosage form is granule.Investigate simultaneously affecting the technological parameter of quality of the pharmaceutical preparations correlative factor in the technique.
Medicine of the present invention is oral drugs, and the granule specification is every bag of packed 6g, day dose: one time 2 bags, 3 times on the one.
Compared with prior art, the present invention has following remarkable result:
1, adopts taking the crude drug amount 'Xue Fu Zhu Yu ' granule day and can reaching 76g of gained of the present invention, reach and take the basically identical effect of crude drug amount ancient prescription decoction day.
2, the effective ingredient naringin in the employing gained 'Xue Fu Zhu Yu ' granule of the present invention, peoniflorin, the retention rate of S-A Hydroxysafflor yellow A, ferulic acid is about respectively 51%, 53%, 30%, 46%, approximate with the retention rate of mentioned component in the prepared decoction of identical crude drug amount, and the day dose of above-mentioned effective ingredient also approaches with decoction, has overcome listing similar preparation " decoction patent medicine " defective.
Description of drawings
Fig. 1 is the moisture absorption percentage diagram of 'Xue Fu Zhu Yu ' granule under different humidity.
The specific embodiment
Describe the present invention in detail below in conjunction with the drawings and the specific embodiments.
Embodiment 1
The present embodiment prepares a kind of 'Xue Fu Zhu Yu ' granule, and the crude drug of this 'Xue Fu Zhu Yu ' granule forms and weight ratio is: 12 parts in Semen Persicae; 9 parts on Flos Carthami; 9 parts of Radix Angelicae Sinensis; 9 parts of Radix Rehmanniae; 5 parts of Rhizoma Chuanxiongs; 6 parts of Radix Paeoniae Rubra; 9 parts of Radix Achyranthis Bidentataes; 5 parts of Radix Platycodoniss; 3 parts of Radix Bupleuri; 6 parts of Fructus Aurantiis; 3 parts in Radix Glycyrrhizae specifically may further comprise the steps:
(1) take by weighing in proportion the above-mentioned raw materials medicine, the decocting that adds 4 times of amounts boiled 0.5 hour, got filtrate, and the decocting that adds again 2 times of amounts boils filtration in 0.5 hour, merges gained filtrate twice;
(2) filtrate that step (1) is obtained is reduced pressure under 50 ℃ the condition at-0.05Mpa, is concentrated into weight and is 2 times of crude drug gross weight, gets extractum;
(3) add adjuvant in the extractum that step (2) is obtained, described adjuvant is soluble starch, and adding addition is the adjuvant of 0.10 times of crude drug gross weight, spray drying, spray-dired technological parameter is 180 ℃ of intake air temperatures, and 100 ℃ of air outlet temperature get spray powder;
(4) spray powder that step (3) is obtained is granulated through dry-pressing, and the technological parameter that dry-pressing is granulated is that principal pressure is 4.5Mpa, and charging rate is 325rpm, and roll rotational speed is 70rpm, draws the 'Xue Fu Zhu Yu ' granule.
The relative humidity of whole preparation environment should be controlled at below 66%.
Embodiment 2
The present embodiment prepares a kind of 'Xue Fu Zhu Yu ' granule, and the crude drug of this 'Xue Fu Zhu Yu ' granule forms and weight ratio is: 12 parts in Semen Persicae; 9 parts on Flos Carthami; 9 parts of Radix Angelicae Sinensis; 9 parts of Radix Rehmanniae; 5 parts of Rhizoma Chuanxiongs; 6 parts of Radix Paeoniae Rubra; 9 parts of Radix Achyranthis Bidentataes; 5 parts of Radix Platycodoniss; 3 parts of Radix Bupleuri; 6 parts of Fructus Aurantiis; 3 parts in Radix Glycyrrhizae specifically may further comprise the steps:
(1) take by weighing in proportion the above-mentioned raw materials medicine, the decocting that adds 12 times of amounts boiled 2 hours, got filtrate, and the decocting that adds again 10 times of amounts boils filtration in 2 hours, merges gained filtrate twice;
(2) filtrate that step (1) is obtained is reduced pressure under 100 ℃ the condition at-0.05Mpa, is concentrated into weight and is 4 times of crude drug gross weight, gets concentrated solution;
(3) add adjuvant in the concentrated solution that step (2) is obtained, described adjuvant is soluble starch, and adding addition is the adjuvant of 0.50 times of crude drug gross weight, spray drying, spray-dired technological parameter is 160 ℃ of intake air temperatures, and 90 ℃ of air outlet temperature get spray powder;
(4) spray powder that step (3) is obtained is granulated through dry-pressing, and the technological parameter that dry-pressing is granulated is that principal pressure is 3.5Mpa, and charging rate is 350rpm, and roll rotational speed is 80rpm, draws the 'Xue Fu Zhu Yu ' granule.
The relative humidity of whole preparation environment should be controlled at below 66%.
Embodiment 3
The present embodiment prepares a kind of 'Xue Fu Zhu Yu ' granule, and the crude drug of this 'Xue Fu Zhu Yu ' granule forms and weight ratio is: 12 parts in Semen Persicae; 9 parts on Flos Carthami; 9 parts of Radix Angelicae Sinensis; 9 parts of Radix Rehmanniae; 5 parts of Rhizoma Chuanxiongs; 6 parts of Radix Paeoniae Rubra; 9 parts of Radix Achyranthis Bidentataes; 5 parts of Radix Platycodoniss; 3 parts of Radix Bupleuri; 6 parts of Fructus Aurantiis; 3 parts in Radix Glycyrrhizae specifically may further comprise the steps:
(1) take by weighing in proportion the above-mentioned raw materials medicine, the decocting that adds 10 times of amounts boiled 1 hour, got filtrate, and the decocting that adds again 8 times of amounts boils filtration in 1 hour, merges gained filtrate twice;
(2) filtrate that step (1) is obtained is reduced pressure under 70 ℃ the condition at-0.05Mpa, is concentrated into weight and is 3 times of crude drug gross weight, gets concentrated solution;
(3) add adjuvant in the concentrated solution that step (2) is obtained, described adjuvant is betacyclodextrin, and adding addition is the adjuvant of 0.3 times of crude drug gross weight, spray drying, spray-dired technological parameter is 150 ℃ of intake air temperatures, and 80 ℃ of air outlet temperature get spray powder;
(4) spray powder that step (3) is obtained is granulated through dry-pressing, and the technological parameter that dry-pressing is granulated is that principal pressure is 4Mpa, and charging rate is 300rpm, and roll rotational speed is 50rpm, draws the 'Xue Fu Zhu Yu ' granule.
The relative humidity of whole preparation environment should be controlled at below 66%.
Embodiment 4
The present embodiment prepares a kind of 'Xue Fu Zhu Yu ' granule, and the crude drug of this 'Xue Fu Zhu Yu ' granule forms and weight ratio is: 12 parts in Semen Persicae; 9 parts on Flos Carthami; 9 parts of Radix Angelicae Sinensis; 9 parts of Radix Rehmanniae; 5 parts of Rhizoma Chuanxiongs; 6 parts of Radix Paeoniae Rubra; 9 parts of Radix Achyranthis Bidentataes; 5 parts of Radix Platycodoniss; 3 parts of Radix Bupleuri; 6 parts of Fructus Aurantiis; 3 parts in Radix Glycyrrhizae specifically may further comprise the steps:
(1) take by weighing in proportion the above-mentioned raw materials medicine, the decocting that adds 8 times of amounts boiled 1.5 hours, got filtrate, and the decocting that adds again 6 times of amounts boils filtration in 1.5 hours, merges gained filtrate twice;
(2) filtrate that step (1) is obtained is reduced pressure under 80 ℃ the condition at-0.05Mpa, is concentrated into weight and is 3 times of crude drug gross weight, gets extractum;
(3) extractum that step (2) is obtained carries out spray drying, and spray-dired technological parameter is 150 ℃ of intake air temperatures, and 80 ℃ of air outlet temperature get spray powder;
(4) spray powder that step (3) is obtained is granulated through dry-pressing, and the technological parameter that dry-pressing is granulated is that principal pressure is 4Mpa, and charging rate is 300rpm, and roll rotational speed is 50rpm, draws the 'Xue Fu Zhu Yu ' granule.
The relative humidity of whole preparation environment should be controlled at below 66%.
The preparation technology's of embodiment 5 'Xue Fu Zhu Yu ' granules optimization
According to the character of prescription medical material effective ingredient, adopt extraction process by water, in the Flos Carthami in S-A Hydroxysafflor yellow A, the Radix Paeoniae Rubra in peoniflorin, Radix Angelicae Sinensis ferulic acid in Chuanxiong, the Fructus Aurantii naringin as index components, with four comprehensive retention rates screening Extraction techniques.
(1) S-A Hydroxysafflor yellow A, peoniflorin, naringin content assaying method
Chromatographic condition: with Kromasil C
18Post is immobile phase; Take the mixed solution of methanol and acetonitrile (26:2) as Mobile phase B, 0.7% phosphoric acid is mobile phase D, carries out gradient elution: 0～10min (B25% → 35%, D75% → 65%), 10～30min(B35% → 45%, D65% → 55%); Flow velocity: 1.0mL/min; Detecting wavelength is respectively that S-A Hydroxysafflor yellow A is that 403nm, peoniflorin are that 230nm, naringin are 283nm; Column temperature: 30 ℃; Sample size: 10 μ L.After measured, S-A Hydroxysafflor yellow A content is 1.31% in the flos carthami, and content of paeoniflorin is 4.03% in the Radix Paeoniae Rubra medical material, and naringin content is 4.10% in the Fructus Aurantii medical material, all meets " the regulation that Chinese pharmacopoeia is 2010 editions.
(2) ferulaic acid content assay method
Chromatographic condition: with Kromasil C
18Be immobile phase; Acetonitrile-0.085% phosphoric acid (17:83) is mobile phase, and flow velocity is 1.0ml/min; Column temperature is 35 ℃; The detection wavelength is 316nm; Sample size: 30 μ L.After measured, the Radix Angelicae Sinensis ferulaic acid content is 0.053%, ferulaic acid content is 0.055% in the Ligusticum chuanxiong Hort, all meets " the regulation that Chinese pharmacopoeia is 2010 editions.
1, orthogonal and experiment
The retention rate of S-A Hydroxysafflor yellow A, peoniflorin, ferulic acid, naringin adopts four factors, three horizontal quadrature experimental designs as index in the compound recipe, investigates the impact of soak time, solvent consumption, extraction time, extraction time, and orthogonal trial is as follows:
Table 3 'Xue Fu Zhu Yu ' granule extraction process quadrature factor level
Take by weighing medical material by prescription, test by above-mentioned orthogonal table, measure volume.Measure S-A Hydroxysafflor yellow A, peoniflorin, ferulic acid, naringin content and solid content in the extracting solution, calculate retention rate and the rate of extract.
2, the rate of extract is measured
The accurate extracting solution that is equivalent to 2g crude drug amount of drawing under the orthogonal experiment item is put the weighed evaporating dish of constant weight, and water bath method is put 105 ℃ in baking oven and dried to constant weight, and weighed weight is calculated the rate of extract.
Table 4 'Xue Fu Zhu Yu ' granule orthogonal experiment sample solid yield
| The experiment number | Crude drug amount (g) | Empty ware heavy (g) | Ware+cream heavy (g) | Cream heavy (g) | The rate of extract (%) |
| 1 | 2 | 50.0180 | 50.7289 | 0.7109 | 35.545 |
| 2 | 2 | 53.4449 | 54.2401 | 0.7952 | 39.760 |
| 3 | 2 | 46.7255 | 47.5885 | 0.8630 | 43.150 |
| 4 | 2 | 52.2965 | 53.2134 | 0.9169 | 45.845 |
| 5 | 2 | 54.5887 | 55.2088 | 0.6201 | 31.005 |
| 6 | 2 | 41.6777 | 42.5158 | 0.8381 | 41.905 |
| 7 | 2 | 54.3330 | 55.1621 | 0.8291 | 41.455 |
| 8 | 2 | 53.9758 | 54.8601 | 0.8843 | 44.215 |
| 9 | 2 | 35.0676 | 35.6812 | 0.6136 | 30.680 |
3, S-A Hydroxysafflor yellow A, peoniflorin, naringin, ferulic acid HPLC measure and the Orthogonal experiment results analysis in the extracting solution
Precision measures the suitable extracting solution under the orthogonal experiment item, crosses F type macroporous adsorbent resin (resin volume 20cm
3), be washed to clarification, continue with 70% ethanol elution 50ml, collect pure washing liquid, shake up, microporous filter membrane filters, and according to above-mentioned HPLC content assaying method, calculates the retention rate of S-A Hydroxysafflor yellow A, peoniflorin, naringin, ferulic acid.
Table 5 'Xue Fu Zhu Yu ' granule orthogonal experiment sample HPLC measurement result
Annotate: the standard curve of S-A Hydroxysafflor yellow A is: y=3319.7x-46.271, the standard curve of peoniflorin is: y=1325.1x-101.7, the standard curve of naringin is: y=1468.1x-7.0489 ferulic acid standard curve is y=4581.1x+2.1094, r=0.9999.
Calculate the retention rate of S-A Hydroxysafflor yellow A, peoniflorin, naringin, ferulic acid, convert comprehensive retention rate in Flos Carthami, Radix Paeoniae Rubra, Fructus Aurantii, Radix Angelicae Sinensis, Ligusticum chuanxiong Hort prescription ratio, analyze experimental result.
Comprehensive retention rate=9/35* Flos Carthami retention rate (S-A Hydroxysafflor yellow A retention rate)+6/35* Radix Paeoniae Rubra retention rate (peoniflorin retention rate)+6/35* Fructus Aurantii retention rate (naringin retention rate)+14/35* ferulic acid retention rate (ferulic acid retention rate).
Orthogonal and the experimental data of the screening of table 6 'Xue Fu Zhu Yu ' granule extraction conditions
With intuitive analysis and variance analysis Orthogonal experiment results is estimated respectively.The result is as follows:
Table 7 'Xue Fu Zhu Yu ' granule Orthogonal experiment results statistics (intuitive analysis)
| ? | Soak time (A) | Solvent consumption (B) | Extraction time (C) | Extraction time (D) |
| Average 1 | 58．563 | 56．330 | 52．563 | 47．250 |
| Average 2 | 51．967 | 54．210 | 52．243 | 55．440 |
| Average 3 | 52．397 | 52．387 | 58．120 | 60．237 |
| Differential | 6．596 | 3．943 | 5．877 | 12．987 |
Table 8 'Xue Fu Zhu Yu ' granule Orthogonal experiment results statistics (variance analysis)
| Factor | Sum of square of deviations | Degree of freedom | The F ratio | The F marginal value | Significance |
| Soak time (A) | 81．729 | 2 | 3．497 | 19．000 | ? |
| Solvent consumption (B) | 23．369 | 2 | 1．000 | 19．000 | ? |
| Extraction time (C) | 65．514 | 2 | 2．803 | 19．000 | ? |
| Extraction time (D) | 258．738 | 2 | 11．072 | 19．000 | ? |
| Error | 23．37 | 2 | ? | ? | ? |
By table 7 intuitive analysis result as can be known, the factor that S-A Hydroxysafflor yellow A, peoniflorin, naringin, the comprehensive retention rate of ferulic acid are had the greatest impact is extraction time (D), the difference of extracting twice and extract three times is little, for saving cost, the level of determining extraction time (D) is level 2 (extracting 2 times); Next is soak time (A), and retention rate is the highest under the level of not soaking, so the level of soak time (A) is defined as 1 (not soaking); Extraction time (C) is not remarkable on comprehensive retention rate impact, preferably, and the level 3 that retention rate is the highest (1 hour); Solvent consumption (B) is not remarkable on comprehensive retention rate impact, because extraction time is selected 2 times, preferably, is defined as by-level 2 (10 times, 8 times); Screening determines that most preferred extraction conditions is A according to analysis result
18
2C
3D
2, namely add respectively 10 times, 8 times water extraction twice, each 1 hour.
4, quadrature repeated authentication experiment
In the prescription ratio, take by weighing Semen Persicae, Flos Carthami, Radix Angelicae Sinensis, Radix Rehmanniae, Rhizoma Chuanxiong, Radix Paeoniae Rubra, Radix Achyranthis Bidentatae, Radix Platycodonis, Fructus Aurantii, Radix Bupleuri, Radix Glycyrrhizae ten and be total to simply 76g, the extraction conditions of determining according to above-mentioned orthogonal test screening (is A
18
2C
3D
2) test, extracting solution filters.Measure volume, precision measures an amount of medicinal liquid, crosses F type macroporous adsorptive resins (resin volume 20 cm
3), after the washing clarification, continue with 70% ethanol elution 50ml, collect pure washing liquid, shake up, as need testing solution.HPLC measures the content of S-A Hydroxysafflor yellow A, peoniflorin, naringin, ferulic acid in the extracting solution, measures simultaneously solid content, calculates retention rate and the rate of extract.
The confirmatory experiment solid content result of table 9 'Xue Fu Zhu Yu ' granule orthogonal experiment
| The experiment number | Crude drug amount (g) | Empty ware heavy (g) | Ware+cream heavy (g) | Cream heavy (g) | Yield % |
| Repeat 1 | 2 | 50．0187 | 50．8193 | 0．8006 | 40．03 |
| Repeat 2 | 2 | 46．7271 | 47．5338 | 0．8067 | 40．34 |
In confirmatory experiment, ferulic acid HPLC measures and uses another root Kromasil C instead
18Be immobile phase, other condition is constant, rebulids the standard curve of ferulic acid.
Adopt former ferulic acid reference substance solution, namely every 1ml contains ferulic acid 0.0252mg.
Above-mentioned reference substance solution is sample introduction 2,12 μ l respectively, and parallel sample introduction 2 pins, HPLC are measured the record peak area, and take the amount of ferulic acid as abscissa, peak area is vertical coordinate drawing standard curve, calculates regression equation to be: y=6710.5x-9.11 respectively.
The confirmatory experiment HPLC measurement result of table 10 'Xue Fu Zhu Yu ' granule orthogonal experiment
Repeated experiments result's demonstration, comprehensive retention rate reaches more than 60%, and solid yield is 40%, and this result has repeatability, points out this extraction process route and determines that parameter suits.
According to experimental result, determine that 'Xue Fu Zhu Yu ' granule extraction process is as follows:
In the prescription ratio, take by weighing Semen Persicae 12g, Flos Carthami 9g, Radix Angelicae Sinensis 9g, Radix Rehmanniae 9g, Rhizoma Chuanxiong 5g, Radix Paeoniae Rubra 6g, Radix Achyranthis Bidentatae 9g, Radix Platycodonis 5g, Fructus Aurantii 6g, Radix Bupleuri 3g, Radix Glycyrrhizae 3g pharmaceutical decocting piece, add respectively 10 times, 8 times water extraction twice, each 1 hour.
The embodiment 6 Xiefuzhuyu medicinal liquids study on the stability that is heated
The thickening temperature of decocting liquid and baking temperature are many between 50 → 100 ℃, for investigating temperature to the concentrated impact that reaches composition retention rate in the dry run of medicinal liquid, the compound recipe medicinal liquid is heated at 50 ℃, 60 ℃, 70 ℃, 80 ℃, 100 ℃ respectively, investigate different temperatures to the content influence of S-A Hydroxysafflor yellow A, peoniflorin, naringin, ferulic acid in the medicinal liquid, for the selection of thickening temperature provides reference.
1, sample preparation
Extract the Xiefuzhuyu medical material according to selection process, precision measures suitable 5g crude drug water gaging extract, totally 6 parts.Put respectively in the Rotary Evaporators, decompression (50 ℃) is recycled to thick paste, is divided into 6 parts.Get a copy of it as stock solution, water-soluble to 20ml, cross F type macroporous adsorptive resins (the resin volume 20cm that pretreatment is good
3), be washed to clarification, continue with 70% ethanol elution 50ml, collect pure washing liquid, shake up, microporous filter membrane filters and get final product.All the other 5 parts of a small amount of water of usefulness with its stripping to evaporating dish, putting baking oven is heated 5 hours (constantly add water between dry period and keep the thick paste state) it with 50 ℃, 60 ℃, 70 ℃, 80 ℃, 100 ℃ respectively, take out, put to room temperature, water-soluble to 20ml, cross F type macroporous adsorptive resins (the resin volume 20cm that pretreatment is good
3), be washed to clarification, continue with 70% ethanol elution 50ml, collect pure washing liquid, shake up, microporous filter membrane filters and get final product.
2, HPLC measures and interpretation
According to above-mentioned HPLC content assaying method, get the need testing solution of above-mentioned sample, injection liquid chromatography, parallel sample introduction two pins, the retention rate of calculating S-A Hydroxysafflor yellow A, peoniflorin, naringin, the different heating temperatures of ferulic acid.
The HPLC result of table 11 S-A Hydroxysafflor yellow A, peoniflorin, naringin
The HPLC result of table 12 ferulic acid
The retention rate of each composition in the different heating temperatures of table 13
The result shows: under this experiment condition, thickening temperature is little on the retention rate impact of peoniflorin, naringin in the medicinal liquid; S-A Hydroxysafflor yellow A, ferulic acid are being subjected in the thermal process more than 70 ℃, and retention rate has a declining tendency, and temperature is higher, and the retention rate downward trend is more obvious.Consider, determine that thickening temperature is below 70 ℃.
Embodiment 7 'Xue Fu Zhu Yu ' particle drying technical studies
The drying drying under reduced pressure commonly used or the spray drying that contain unstability composition extractum.
If the employing drying under reduced pressure, medicinal liquid need be concentrated into thick paste, loses more at this process S-A Hydroxysafflor yellow A, ferulic acid.
Medicinal liquid moment is subjected to the spray drying of heated drying, allows relatively rare medicinal liquid.Through attempting, medicinal liquid is concentrated into medicinal liquid than being 1:3, measure the rate of extract, add soluble starch or betacyclodextrin, can carry out smoothly, this route can be avoided the composition degraded in the further concentration process of thick solution.Below measure by experiment spray drying step composition retention rate.
Get 'Xue Fu Zhu Yu ' granule concentrated solution, measure the rate of extract, add soluble starch 2.26kg, mix homogeneously carries out spray drying.Through investigating, intake air temperature 150-180 ℃, 80-100 ℃ of air outlet temperature can be carried out smoothly.The gained dried cream powder keeps sample.
Measure respectively concentrated solution and spray drying middle finger index composition content, the theory of computation gets part total amount and index components retention rate, and the result is as follows:
Each processing step product of table 14 is weighed respectively and is kept sample
| The experiment title | Gross weight/kg |
| Concentrated solution | 35.5 |
| Dried cream powder | 6.512 |
Each composition reservation amount in table 15 spray-drying process
*Must measure in the spray powder theory
The comparison of each Theory of Components content and actual content in table 16 spray drying powder
Each composition retention rate of table 17 spray drying
Experimental result shows: hydroxyl-removal safflower yellow A retention rate is 75% in spray-drying process, and naringin, peoniflorin and ferulic acid show that all more than 85% selected drying process is feasible, reasonably.
The research of embodiment 8 'Xue Fu Zhu Yu ' granule formation technologies
1, dry-pressing granulating process screening
If the conventional wet granulation of employing industry can cause the degraded of thermal instability effective ingredient.Therefore determine to adopt dry-pressing to granulate.The experience of being granulated by dry-pressing is as can be known: extract powder moisture is high, easy caking, easily sticking machine in the production; Nip pressure is little, and tabletting is loose; Nip pressure is larger, easily glues machine, and the granule melting is bad; Roll rotational speed is fast, and sheet is loose.Nip pressure and extractum water content are the principal elements that affects dry-pressing granulation granular mass.'Xue Fu Zhu Yu ' spray drying medicated powder water content is about 2.0%, and mouthfeel is suitable, attempts directly dry-pressing through preliminary experiment and granulates.
Charging rate, pressure roller rotating speed, principal pressure technological parameter are investigated, got spray drying medicated powder, carry out dry-pressing, make 12～40 purpose granules at GK-100G type dry-pressing granulator (Jiangsu rarity instrument factory).And carry out following the effects, experimental result is as follows.
The impact of table 18 dry-pressing grain made parameter-principal pressure
Table 19 dry-pressing grain made parameter-roll rotational speed and charging rate impact
Result's demonstration, optimum dry-pressing grain made parameter is: charging rate is 300rpm, and the pressure roller rotating speed is 50rpm, and principal pressure is 4MPa..
2, the critical humidity research of granule
With the particle drying that makes to constant weight, the approximately thick granule of 2mm is put in weighing botle bottom in constant weight, accurately weighing is placed on the exsiccator interior (the weighing bottle cap is opened) of the listed supersaturated solution that fills respectively 7 kinds of different salt, the moisture absorption percentage rate is calculated in weighing behind the maintenance 72h in 25 ℃ of constant incubators.Take the moisture absorption percentage data as vertical coordinate, the relative humidity data are abscissa mapping, the results are shown in Table 20 and Fig. 1.
Moisture absorption percentage rate behind the table 20 granule 72h under different relative humiditys (25 ℃)
| Saturated brine | Potassium acetate | Magnesium chloride | Potassium carbonate | Sodium bromide | Potassium iodide | Sodium chloride | Potassium chloride |
| RH％ | 33 | 43 | 51 | 59 | 74 | 81 | 97 |
| Hydroscopicity % | 3.31 | 5.41 | 7.22 | 9.93 | 16.01 | 21.68 | 34.34 |
Critical relative humidity is medicine moisture absorption whether marginal value, ambient humidity when determining to produce according to it, by table 20 take the moisture absorption percentage rate as vertical coordinate, relative humidity is abscissa, obtain sucting wet curve (asking for an interview Fig. 1), do tangent line at the two ends of curve respectively, abscissa corresponding to two points of intersection of tangents is critical relative humidity.As seen from the experiment, the critical relative humidity of granulation is 66%, therefore when producing this preparation, the relative humidity of workshop condition should be controlled at below 66%, points out simultaneously the storage requirement of this product also should meet this requirement.
3, the investigation of granularity
Get 'Xue Fu Zhu Yu ' granule 30g, weighed weight, put No. one and No. five medicines sieve in, keep level to sieve, about come and go, the limit sieves 3 minutes, getting can not be by sieve and can be by granule and the powder that sieves for No. five, weighed weight, get 2.7g, percentage is 9.0%, and is up to specification.
4, the investigation of angle of repose
Measure angle of repose with the device that 2 funnel dislocation are together in series, the diameter d of measuring culture dish is 6.1cm, and radius r is 3.05cm.Slowly inject up the 'Xue Fu Zhu Yu ' granule in the triangular funnel, automatically flow out the culture dish edge with powder, and form till the more stable cone-shaped pile of grounds, measuring cone height h is 2.4cm, calculate angle of repose that (tan α=h/r) is 38 degree, the more flowability of granule.
The effective retention rate research of embodiment 9 pilot processes
1, pilot process flow process
In the prescription ratio, take by weighing Semen Persicae 5.30kg, Flos Carthami 4.00kg, Radix Paeoniae Rubra 2.70kg, Radix Angelicae Sinensis 4.00kg, Rhizoma Chuanxiong 2.20kg, Radix Achyranthis Bidentatae 4.00kg, Fructus Aurantii 2.70kg, Radix Bupleuri 1.30kg, Radix Platycodonis 2.20kg, Radix Rehmanniae 4.00kg, Radix Glycyrrhizae 1.30kg, medical material always feeds intake and is 33.70kg, decoct with water twice, adding for the first time 10 times of water gagings decocted 1 hour, filter, weighing keeps sample; Add for the second time 8 times of water gagings and decocted 1 hour, filter, weighing keeps sample; Merging filtrate, weighing keeps sample; Decompression (0.05Mpa is about 60 ℃) is concentrated into 1:3(medical material and amount of liquid medicine), weighing keeps sample; Centrifugal, weighing keeps sample; Add soluble starch 3.51kg, mix homogeneously carries out spray drying, and dried cream powder is weighed.
Each processing step product of table 21 is weighed respectively and is kept sample
| Title | Gross weight/kg |
| Extracting solution for the first time | 216·84 |
| Extracting solution for the second time | 202.42 |
| Merge extractive liquid, | 419.26 |
| Concentrated solution (1:3) | 97.22 |
| After concentrated solution is centrifugal | 94.56 |
| Dried |
15·01 |
2, pilot process respectively goes on foot the preparation of product need testing solution
2.1 for the first time preparation of extracting solution need testing solution
Get the extracting solution first time that is equivalent to 5.00g crude drug amount, accurately weighed (30.8860g, 30.8832g) is after (the 1.3cm * 15cm) of pretreated F type macroporous adsorptive resins, be washed to the effluent clarification, continue and use 80% ethanol elution, collect 80% ethanol elution to 100ml measuring bottle scale, low-temperature reduced-pressure is recycled to approximately 15ml, be transferred to the 25ml measuring bottle, add 70% ethanol dilution to scale, shake up, filter, get subsequent filtrate, and get final product.
2.2 for the second time preparation of extracting solution need testing solution
Get the extracting solution second time that is equivalent to 5.00g crude drug amount, accurately weighed (28.8354g, 28.8301g) is after (the 1.3cm * 15cm), be washed to the effluent clarification of pretreated F type macroporous adsorptive resins, continue and use 80% ethanol elution, collect 80% ethanol elution to 100ml measuring bottle scale, low-temperature reduced-pressure is recycled to approximately 15ml, is transferred to the 25ml measuring bottle, add 70% ethanol dilution to scale, shake up, get subsequent filtrate, and get final product.
2.3 the preparation of merge extractive liquid, need testing solution
Get the merge extractive liquid, that is equivalent to 5.00g crude drug amount, accurately weighed (59.7251g, 59.7242g) is after (the 1.3cm * 15cm), be washed to the effluent clarification of pretreated F type macroporous adsorptive resins, continue and use 80% ethanol elution, collect 80% ethanol elution to 100ml measuring bottle scale, low-temperature reduced-pressure is recycled to approximately 20ml, is transferred to the 50ml measuring bottle, add 70% ethanol dilution to scale, shake up, get subsequent filtrate, and get final product.
2.4 the preparation of concentrated solution need testing solution
Get the concentrated solution that is equivalent to 5.00g crude drug amount, accurately weighed (13.8453g, 13.8427g) is after (the 1.3cm * 15cm), be washed to the effluent clarification of pretreated F type macroporous adsorptive resins, continue and use 80% ethanol elution, collect 80% ethanol elution to 100ml measuring bottle scale, low-temperature reduced-pressure is recycled to approximately 20ml, is transferred to the 50ml measuring bottle, add 70% ethanol dilution to scale, shake up, get subsequent filtrate, and get final product.
2.5 the preparation of centrifugal rear medicinal liquid need testing solution
Get the centrifugal rear medicinal liquid that is equivalent to 5.00g crude drug amount, accurately weighed (13.4724g, 13.4727g) is after (the 1.3cm * 15cm), be washed to the effluent clarification of pretreated F type macroporous adsorptive resins, continue and use 80% ethanol elution, collect 80% ethanol elution to 100ml measuring bottle scale, low-temperature reduced-pressure is recycled to approximately 20ml, is transferred to the 50ml measuring bottle, add 70% ethanol dilution to scale, shake up, get subsequent filtrate, and get final product.
2.6. the preparation of spray powder (drying tower wall) need testing solution
Get and be equivalent to 50g crude drug amount dried cream powder, accurately weighed (22.5030g), add suitable quantity of water and make dissolving, be transferred in the 200ml measuring bottle, thin up shakes up to scale, and precision measures 20ml, after (the 1.3cm * 15cm) of pretreated F type macroporous adsorptive resins, be washed to the effluent clarification, continue and use 80% ethanol elution, collect 80% ethanol elution to 100ml measuring bottle scale, low-temperature reduced-pressure is recycled to approximately 20ml, be transferred to the 50ml measuring bottle, add 70% ethanol dilution to scale, shake up, get subsequent filtrate, and get final product.
2.7 the preparation of spray powder (receiving flask) need testing solution
Get and be equivalent to 50g crude drug amount dried cream powder, accurately weighed (22.5054g), add suitable quantity of water and make dissolving, be transferred in the 200ml measuring bottle, thin up shakes up to scale, and precision measures 20ml, after (the 1.3cm * 15cm) of pretreated F type macroporous adsorptive resins, be washed to the effluent clarification, continue and use 80% ethanol elution, collect 80% ethanol elution to 100ml measuring bottle scale, low-temperature reduced-pressure is recycled to approximately 20ml, be transferred to the 50ml measuring bottle, add 70% ethanol dilution to scale, shake up, get subsequent filtrate, and get final product.
2.8 the preparation of spray powder (after merging) need testing solution
Get and be equivalent to 50g crude drug amount dried cream powder, accurately weighed (22.5013g), add suitable quantity of water and make dissolving, be transferred in the 200ml measuring bottle, thin up shakes up to scale, and precision measures 20ml, after (the 1.3cm * 15cm) of pretreated F type macroporous adsorptive resins, be washed to the effluent clarification, continue and use 80% ethanol elution, collect 80% ethanol elution to 100ml measuring bottle scale, low-temperature reduced-pressure is recycled to approximately 20ml, be transferred to the 50ml measuring bottle, add 70% ethanol dilution to scale, shake up, get subsequent filtrate, and get final product.
3, centrifugal rear the rate of extract is measured
Get the centrifugal rear medicinal liquid that is equivalent to 5g crude drug amount, accurately weighed, put the weighed evaporating dish of constant weight, water bath method is put 105 ℃ in baking oven and is dried to constant weight, and weighed weight is calculated the rate of extract.
The centrifugal rear dried cream yield of table 22 concentrated solution
3.1. spray drying gets powder
Table 23 spray drying gets powder
4, HPLC measures and interpretation
4.1 peoniflorin, naringin, S-A Hydroxysafflor yellow A and ferulic acid HPLC condition determination
4.1.1 peoniflorin, naringin and S-A Hydroxysafflor yellow A HPLC condition determination
With Kromasil C
18Post is immobile phase; Take the mixed solution of methanol and acetonitrile (26:2) as Mobile phase B, 0.7% phosphoric acid is mobile phase D, and according to the form below carries out gradient elution, flow velocity: 1.0mL/min; Detecting wavelength is respectively that S-A Hydroxysafflor yellow A is that 403nm, peoniflorin are that 230nm, naringin are 283nm; Column temperature: 30 ℃.
Table 24 eluent gradient elution time table
| Time/min | Mobile phase B/% | Mobile phase D/% |
| 0 | 25 | 75 |
| 10 | 35 | 65 |
| 30 | 45 | 55 |
| 33 | 25 | 75 |
| 36 | 25 | 75 |
4.1.2 ferulic acid HPLC condition determination
With Kromasil C
18Post is immobile phase; Take the phosphoric acid solution (18:82) of acetonitrile-0.085% as mobile phase, flow velocity: 1.0mL/min; The detection wavelength is 316nm;
4.2 the foundation of peoniflorin, naringin, S-A Hydroxysafflor yellow A and ferulic acid standard curve
4.2.1 peoniflorin, naringin mix the preparation of reference substance solution and the drafting of standard curve
Get peoniflorin and naringin is an amount of, accurately weighed, be mixed with every 1ml and contain peoniflorin 0.265mg, and the mixed solution of naringin 0.061mg.
Accurate peoniflorin, naringin mixing reference substance solution 2,2,20, the 20 μ l injection liquid chromatographies drawn, the record peak area, take the amount of naringin, peoniflorin as abscissa, peak area is vertical coordinate drawing standard curve respectively, calculate regression equation, the result is as follows:
Table 25 naringin standard curve
| Sampling volume/μ l | Sample introduction quality/μ g | Peak area |
| 2 | 0.122 | 200248 |
| 2 | 0.122 | 213334 |
| 20 | 1·22 | 2161260 |
| 20 | 1.22 | 2164166 |
Table 26 peoniflorin standard curve
| Sampling volume/μ l | Sample introduction quality/μ g | Peak area |
| 2 | 0·5300 | 677413 |
| 2 | 0.5300 | 716621 |
| 20 | 55.3000 | 7352006 |
| 20 | 5.3000 | 7357557 |
The regression equation of naringin is: y=1781349.73x – 10533.67.
The regression equation of peoniflorin is: y=1395757.76x – 42734.61.
4.2.2 the drafting of S-A Hydroxysafflor yellow A standard curve
Get S-A Hydroxysafflor yellow A an amount of, accurately weighed, be mixed with the solution that every 1ml contains 0.148mg.
Accurate S-A Hydroxysafflor yellow A reference substance solution 2,2,20, the 20 μ l injection liquid chromatographies of drawing, the record peak area, take the amount of S-A Hydroxysafflor yellow A as abscissa, peak area is vertical coordinate drawing standard curve, calculates regression equation respectively, the result is as follows:
Table 27 S-A Hydroxysafflor yellow A standard curve
| Sampling volume/μ l | Sample introduction quality/μ g | Peak area |
| 2 | 0·296 | 690437 |
| 2 | 0·296 | 678531 |
| 20 | 2·96 | 7090858 |
| 20 | 2.96 | 7078956 |
The regression equation of S-A Hydroxysafflor yellow A is: y=2402561.19x-26674.11,
4.2.3 the drafting of ferulic acid standard curve
Get ferulic acid an amount of, accurately weighed, be mixed with the solution that every 1ml contains 0.0244mg.
Accurate ferulic acid reference substance solution 2,2,20, the 20 μ l injection liquid chromatographies of drawing, the record peak area, take the amount of ferulic acid as abscissa, peak area is vertical coordinate drawing standard curve, calculates regression equation respectively, the result is as follows:
Table 28 ferulic acid standard curve
| Sampling volume/μ l | Sample introduction quality/μ g | Peak area |
| 2 | 0.0488 | 375406 |
| 2 | 0·0488 | 376628 |
| 20 | 0·488 | 3817342 |
| 20 | 0·488 | 3816379 |
The regression equation of ferulic acid is: y=7834343.12x-6298.94.
4.3.HPLC measurement result
Table 29 sample pretreatment
| The experiment title | Crude drug amount/kg | Medicinal liquid gross weight/kg | Sampling amount/g | Constant volume/ml |
| Extract 1-1 | 33.7 | 216.84 | 30.8860 | 25 |
| Extract 1-2 | 33.7 | 216·84 | 30.8832 | 25 |
| Extract 2-1 | 33.7 | 202.42 | 28.8354 | 25 |
| Extract 2-2 | 33·7 | 202.42 | 28.8301 | 25 |
| Amalgamation liquid 1 | 33.7 | 419.26 | 59.7251 | 50 |
| Amalgamation liquid 2 | 33.7 | 419.26 | 59.7242 | 50 |
| Concentrated solution 1 | 33·7 | 97.22 | 13.8453 | 50 |
| Concentrated solution 2 | 33.7 | 97.22 | 13.8427 | 50 |
| Centrifugal rear 1 | 33.7 | 94.56 | 13.4724 | 50 |
| Centrifugal rear 2 | 33.7 | 94.56 | 13.4727 | 50 |
Table 30 sample pretreatment (spray drying powder)
Table 31 experimental result (naringin and peoniflorin)
Table 32 experimental result (S-A Hydroxysafflor yellow A and ferulic acid)
Experimental result shows: the lower extraction ratio of trial work skill is all higher hereinto for index components naringin, peoniflorin, S-A Hydroxysafflor yellow A and the ferulic acid in the compound recipe, be respectively 78%, 56%, 58% and 69%, and have no obvious loss in follow-up concentrating under reduced pressure, centrifuging process, illustrate that the pilot process that adopts is reasonable.
Table 33 spray powder (naringin and peoniflorin)
Table 34 spray powder (S-A Hydroxysafflor yellow A and ferulic acid)
Experimental result shows: compare with each composition retention rate peoniflorin 50%, naringin 74%, S-A Hydroxysafflor yellow A 59% and ferulic acid 57% in the centrifugal rear medicinal liquid, outside the hydroxyl-removal safflower yellow A retention rate less loss 23%, peoniflorin, ferulic acid and naringin retention rate change little, illustrate that this technique is reasonable, feasible.
Each composition reservation amount in table 35 spray-drying process
*In the spray powder theory must measure with receiving flask in component content
(1) in the upper table 35, (2) pilot scale spray powder for obtaining under the same process conditions, the data of employing crosspointer input mode gained are to investigate the impact that each composition is kept with regard to spray-drying process.
Each composition retention rate in table 36 spray-drying process
*The reservation amount sees Table 12 in the spray powder
The comparison of each Theory of Components content and actual content in table 37 spray drying powder
Experimental result shows: in the spray powder theory must measure with receiving flask in sample size, although each index components is all lost in spray process, but most of retention rate is higher, hydroxyl-removal safflower yellow A low outer (60%), naringin, peoniflorin and ferulic acid are all more than 80%, the most of composition in the compound recipe medicinal liquid is retained in the spray-drying process as can be known, proves that designed drying process is feasible, reasonably.
Annotate: retention rate=spray powder actual content/spray powder theoretical content * 100%
Spray powder theoretical content=centrifugal rear medicinal liquid index components total amount (mg)/spray powder theory must be measured (g)
The spray powder theory must be measured=inventory * the rate of extract+adjuvant amount
The spray powder actual content is obtained by the HPLC measure and calculation
Under above-mentioned optimization dry-pressing grain made parameter, the gained spray powder divides and carries out dry-pressing for three times and granulate: charging rate is 300rpm, the pressure roller rotating speed is 50rpm, principal pressure is 4Mpa., the preparation granule, get granule 10.2kg(lot number 091225), 2.02kg(lot number 091226), 2.0kg(lot number 091227).
Table 38 'Xue Fu Zhu Yu ' granule contains survey (naringin retention rate)
Table 39 'Xue Fu Zhu Yu ' granule is for containing survey (peoniflorin retention rate)
Table 40 'Xue Fu Zhu Yu ' granule contains survey (S-A Hydroxysafflor yellow A retention rate)
Table 41 'Xue Fu Zhu Yu ' granule contains survey (ferulic acid retention rate)
*Must measure as granule and must measure in the spray powder theory
The result shows: in the assay of 'Xue Fu Zhu Yu ' granule, naringin, peoniflorin, the retention rate of S-A Hydroxysafflor yellow A and ferulic acid is about respectively 51%, 53%, 30% and 46%, with the retention rate no significant difference of each index components of powder in the 'Xue Fu Zhu Yu ' dried cream powder before the molding.
The comparison of embodiment 10 'Xue Fu Zhu Yu ' granules and decoction index components day dose
Prepare the gained granule with above-mentioned technique, measure wherein index components naringin, peoniflorin, S-A Hydroxysafflor yellow A and ferulaic acid content calculate day and take the index components amount; And with same crude drug amount with batch medical material according to conventional preparation gained decoction relatively, the result shows that index components day dose is similar to (seeing Table 42) with decoction
Table 42 is with the comparison of batch medical material 'Xue Fu Zhu Yu ' granule and decoction index components day dose
As can be seen from the above table, adopt the effective ingredient naringin in the gained 'Xue Fu Zhu Yu ' granule of the present invention, peoniflorin, the day dose of S-A Hydroxysafflor yellow A, ferulic acid all obviously is better than other commercially available capsules, granule, oral liquid, and approximate with the day dose of mentioned component in the prepared decoction of identical crude drug amount, overcome listing similar preparation " decoction patent medicine " defective.
Should be noted that at last; above embodiment is only in order to illustrate technical scheme of the present invention but not limiting the scope of the invention; although with reference to preferred embodiment the present invention has been done detailed description; those of ordinary skill in the art is to be understood that; can make amendment or be equal to replacement technical scheme of the present invention, and not break away from essence and the scope of technical solution of the present invention.
Claims (10)
1. the preparation method of a 'Xue Fu Zhu Yu ' granule, the crude drug of described 'Xue Fu Zhu Yu ' granule forms and weight ratio is: Semen Persicae 11-13 part; Flos Carthami 8-10 part; Radix Angelicae Sinensis 8-10 part; Radix Rehmanniae 8-10 part; Rhizoma Chuanxiong 4-6 part; Radix Paeoniae Rubra 5-7 part; Radix Achyranthis Bidentatae 8-10 part; Radix Platycodonis 4-6 part; Radix Bupleuri 2-4 part; Fructus Aurantii 5-7 part; Radix Glycyrrhizae 2-4 part is characterized in that, may further comprise the steps:
(1) takes by weighing in proportion the above-mentioned raw materials medicine, add the decocting that 4-12 doubly measures and boiled 0.5-2 hour, get filtrate, add again the decocting that 2-10 doubly measures and boil filtration in 0.5-2 hour, merge gained filtrate twice;
(2) filtrate that step (1) is obtained is reduced pressure under 50-80 ℃ the condition at-0.05Mpa, is concentrated into weight and is the 2-4 of crude drug gross weight doubly, gets extractum or concentrated solution;
(3) add adjuvant in the extractum that step (2) is obtained or the concentrated solution, described adjuvant is soluble starch or betacyclodextrin, and the 0-0.50 that described adjuvant addition is the crude drug gross weight times, spray drying gets spray powder;
(4) spray powder that step (3) is obtained is granulated, and get final product.
2. the preparation method of 'Xue Fu Zhu Yu ' granule according to claim 1 is characterized in that, described step takes by weighing described crude drug in (1) in proportion, adding 10 times of water gagings decocted 1 hour, get filtrate, add again 8 times of water gagings and decoct filtration in 1 hour, merge gained filtrate twice.
3. the preparation method of 'Xue Fu Zhu Yu ' granule according to claim 1 is characterized in that, the technological parameter of filtrate decompression is 50-70 ℃ in the described step (2).
4. the preparation method of 'Xue Fu Zhu Yu ' granule according to claim 1 is characterized in that, spray-dired technological parameter is in the described step (3): intake air temperature 150-180 ℃, and 80-100 ℃ of air outlet temperature.
5. the preparation method of 'Xue Fu Zhu Yu ' granule according to claim 4 is characterized in that, spray-dired technological parameter is in the described step (3): 150 ℃ of intake air temperatures, 80 ℃ of air outlet temperature.
6. the preparation method of 'Xue Fu Zhu Yu ' granule according to claim 1, it is characterized in that, spray powder is granulated through dry-pressing in the described step (4), and the technological parameter that dry-pressing is granulated is that principal pressure is 3.5-4.5Mpa, charging rate is 300-350rpm, and roll rotational speed is 50-80rpm.
7. the preparation method of 'Xue Fu Zhu Yu ' granule according to claim 6 is characterized in that, the technological parameter that dry-pressing is granulated in the described step (4) is that principal pressure is 4Mpa, and charging rate is 300rpm, and roll rotational speed is 50rpm.
8. 'Xue Fu Zhu Yu ' granule of each preparation method gained according to claim 1-7.
9. 'Xue Fu Zhu Yu ' granule according to claim 8 is characterized in that, taking the crude drug amount day of this 'Xue Fu Zhu Yu ' granule is 76 grams.
10. 'Xue Fu Zhu Yu ' granule according to claim 8 is characterized in that, its crude drug forms and weight ratio is: 12 parts in Semen Persicae; 9 parts on Flos Carthami; 9 parts of Radix Angelicae Sinensis; 9 parts of Radix Rehmanniae; 5 parts of Rhizoma Chuanxiongs; 6 parts of Radix Paeoniae Rubra; 9 parts of Radix Achyranthis Bidentataes; 5 parts of Radix Platycodoniss; 3 parts of Radix Bupleuri; 6 parts of Fructus Aurantiis; 3 parts in Radix Glycyrrhizae.
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|---|---|---|---|---|
| CN105194072A (en) * | 2015-11-04 | 2015-12-30 | 江苏省中医药研究院 | Traditional Chinese medicine composition with efficacy of assisting in treatment of pulmonary infection |
| CN106619996A (en) * | 2017-03-15 | 2017-05-10 | 佛山市弘泰药物研发有限公司 | Chinese patent medicine for nourishing blood for regulating menstruation and preparation process thereof |
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| CN103356796B (en) | 2015-07-22 |
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