CN1657093A - Preparation method of granular agent for raising leucocyte and its quality control method - Google Patents
Preparation method of granular agent for raising leucocyte and its quality control method Download PDFInfo
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- CN1657093A CN1657093A CN 200410078100 CN200410078100A CN1657093A CN 1657093 A CN1657093 A CN 1657093A CN 200410078100 CN200410078100 CN 200410078100 CN 200410078100 A CN200410078100 A CN 200410078100A CN 1657093 A CN1657093 A CN 1657093A
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- 238000002360 preparation method Methods 0.000 title claims description 33
- 239000003814 drug Substances 0.000 claims abstract description 24
- 229930003944 flavone Natural products 0.000 claims abstract description 19
- 235000011949 flavones Nutrition 0.000 claims abstract description 19
- 239000000463 material Substances 0.000 claims abstract description 17
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 claims abstract description 16
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 claims abstract description 16
- 229940114124 ferulic acid Drugs 0.000 claims abstract description 16
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 claims abstract description 16
- 235000001785 ferulic acid Nutrition 0.000 claims abstract description 16
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000001694 spray drying Methods 0.000 claims abstract description 10
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- 150000002212 flavone derivatives Chemical class 0.000 claims abstract description 8
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 51
- 239000008187 granular material Substances 0.000 claims description 44
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- TZJALUIVHRYQQB-XLRXWWTNSA-N icariin Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-XLRXWWTNSA-N 0.000 claims description 19
- TZJALUIVHRYQQB-UHFFFAOYSA-N icariine Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(C)O2)O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-UHFFFAOYSA-N 0.000 claims description 19
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- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 claims description 3
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- RNJITZXZQQNIMB-UHFFFAOYSA-N OC=O.ClCCl.CCOC(C)=O Chemical compound OC=O.ClCCl.CCOC(C)=O RNJITZXZQQNIMB-UHFFFAOYSA-N 0.000 claims description 3
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- XXMFJKNOJSDQBM-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;hydrate Chemical compound [OH3+].[O-]C(=O)C(F)(F)F XXMFJKNOJSDQBM-UHFFFAOYSA-N 0.000 claims description 2
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- 201000002364 leukopenia Diseases 0.000 abstract description 4
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Images
Abstract
A Chinese medicine in the form of effervescent particles for treating the leukocytopenia caused by radiotherapy and chemicotherapy is prepared from 11 Chinese-medicinal materials including epimedium, etc and beta-cyclodextrin through extracting, dissolving, spray drying and granulating. Its quality control method features the content of wolfberry fruit, Chinese angelica root, icaritin, ferulic acid and general flavone are measured.
Description
(technical field)
Living BAIPAO of the present invention is risen granule and is related to a kind of warming the kidney and strengthening the spleen that has, the benefiting vital QI and blood effect, be used for the treatment of that cancer is put, leukopenia caused by cancer chemotherapy belongs to deficiency of spleen-YANG and kidneyYANG, medicine of insufficiency of vital energy and blood patient and preparation method thereof, method of quality control belong to the field of Chinese medicines.
(background technology)
Serious day by day along with modern society environment and food pollution, cancer morbidity is more and more higher, and the treatment cancer mainly adopt put, the means of chemotherapy, but its side effect is very big, wherein the overwhelming majority can cause leukopenia, this disease is by deficiency of spleen-YANG and kidneyYANG, and insufficiency of vital energy and blood and causing is a kind of commonly encountered diseases, frequently-occurring disease.Also do not have in the modern chemistry medicine a kind of safe, treat the long-term prescription of this disease efficiently.And Chinese medicine is characteristic with many active component, many target spots drug effect, be good at treatment, nurse one's health ill physiological function, and can be for taking for a long time.Develop the Chinese medicine traditional advantage, develop preparation stabilization, drug safety, dosage is accurate, quality controllable, the reliable Chinese medicine preparation of curative effect is significant.
Chinese medicine raw white kalgan lamb skin clothes liquid is a kind ofly to be used for the treatment of that cancer is put, leukopenia caused by cancer chemotherapy belongs to deficiency of spleen-YANG and kidneyYANG, the Chinese medicine patent medicine preparation of insufficiency of vital energy and blood patient, make by main material medicine Herba Epimedii, Fructus Psoraleae, Radix Aconiti Lateralis Preparata (system), Fructus Lycii, the Radix Astragali, Caulis Spatholobi, Radix Rubiae, Radix Angelicae Sinensis, Rhizoma Phragmitis, Radix Ophiopogonis, Radix Glycyrrhizae etc., has warming the kidney and strengthening the spleen, the benefiting vital QI and blood effect.Herba Epimedii, Fructus Psoraleae, the Radix Astragali, Radix Glycyrrhizae and Caulis Spatholobi contain flavone compound in the side.Active component is the basis of its curative effect in the said preparation: the flavone that Herba Epimedii contains have the effect that strengthens humoral immune function (Sun Yi. the immunopharmacology research recent developments of Herba Epimedii and extract thereof. the journal .1995.18 of Chengdu University of Traditional Chinese Medicine (4) .49-52); Radix Astragali total flavones to radiogenic immune system injury in the radiotherapy art have the certain protection effect (Lin Shanwen etc. Radix Astragali total flavones in art during radiotherapy to the laboratory observation of immunity of organisms influence. the journal .1995.1.5 of medical officer college of continuing education).Radix Angelicae Sinensis contains effective ingredient such as organic acid such as ferulic acid, experimental results show that the contained ferulic acid of Radix Angelicae Sinensis can obviously promote mice carbon clearance and peritoneal macrophage to engulf chicken red blood cell, the human body immunity improving function (Feng Junzhi. State of Zhao is flat. the immune pharmacology progress of Radix Angelicae Sinensis. Fujian Chinese medicine .2003.34 (3) .49); Put in the treatment cancer, in the chemotherapy operation, the raising of immunologic function is very important.
At present, said preparation is a liquid preparation, and its preparation process falls behind.For clarity is guaranteed, before embedding, with 20% sodium hydroxide solution adjust pH to 7, ferulic acid is very unstable behind the salify when pH7, is easy to failure loss in liquid.For guaranteeing the clarification of liquid preparation, need operations such as cold preservation, filtration during preparation, the effective ingredient of a part of poorly water-soluble can be precipitated out and lose, and can descend significantly as flavones ingredient content.The solvent of preparation is a water, and medicine stability wherein is poor, and the effective ingredient of some poorly water-solubles also can be precipitated out in storage, causes active constituent content to reduce, and curative effect can not get guaranteeing.Therefore, raw white kalgan lamb skin clothes liquid does not meet reliable, the quality controllable requirement of modern medicines curative effect.
(summary of the invention)
One of the object of the invention provides the living BAIPAO of a kind of Chinese medicine and rises granule; Two of purpose provides a kind of Chinese medicine and gives birth to the preparation method that BAIPAO is risen granule.Three of purpose provides Chinese medicine and gives birth to the method for quality control that BAIPAO is risen granule.
The present invention obeys liquid with raw white kalgan lamb skin and changes effervescent granule (solid preparation) into, adopt advanced technologies, need not 20% sodium hydroxide solution adjust pH hydrotropy, but add the beta-schardinger dextrin-hydrotropy after alcohol deposit fluid reclaimed ethanol, make the flavonoids effective constituent of poor solubility keep more, medicinal liquid carries out spray drying again, and dry granulation has been avoided the loss of ferulic acid, flavones ingredient.Keep effective ingredient effectively, improved our curative effect.
" give birth to BAIPAO and rise granule " of the present invention is specific as follows:
The present invention's " give birth to BAIPAO rise granule " is that crude drug is made by 240 weight portion Herba Epimedii, 120 weight portion Fructus Psoraleaes, 80 weight portion Radix Aconiti Lateralis Preparatas (system), 240 weight portion Fructus Lycii, the 240 weight portion Radixs Astragali, 240 weight portion Caulis Spatholobis, 240 weight portion Radix Rubiaes, 120 weight portion Radix Angelicae Sinensis, 240 weight portion Rhizoma Phragmitiss, 120 weight portion Radix Ophiopogonis, 120 weight portion Radix Glycyrrhizaes; Medicament also contains cosolvent beta-schardinger dextrin-10-50 weight portion; Contain correctives steviosin 0.67 weight portion, contain disintegrating agent carboxymethyl base Starch Sodium 16 weight portions; Contain forming agent dextrin 21 weight portions, contain effervescent 20 weight portions, this effervescent is by citric acid, and sodium carbonate and sodium bicarbonate are formed.
The present invention gives birth to BAIPAO and rises particulate preparation method as follows:
Take by weighing 240 weight portion Herba Epimedii, 120 weight portion Fructus Psoraleaes, 80 weight portion Radix Aconiti Lateralis Preparatas (system), 240 weight portion Fructus Lycii, the 240 weight portion Radixs Astragali, 240 weight portion Caulis Spatholobis, 240 weight portion Radix Rubiaes, 120 weight portion Radix Angelicae Sinensis, 240 weight portion Rhizoma Phragmitiss, 120 weight portion Radix Ophiopogonis, 120 weight portion Radix Glycyrrhizaes, standby;
More than ten simply, decoct with water secondary, each 1 hour, collecting decoction filters, and filtrate decompression is concentrated into relative density 1.24～1.27 (25 ℃), add ethanol and make and contain alcohol amount and reach 70%, left standstill 12～36 hours, filter, filtrate recycling ethanol adds cosolvent beta-schardinger dextrin-10-50 weight portion, and 60 ℃ were stirred 30 minutes-2 hours, be concentrated into relative density 1.08-1.12 (50 ℃), filter spray drying, inlet temperature 160-190 ℃, leaving air temp 60-90 ℃, get spray powder.Add-on type agent dextrin 21 weight portions add correctives steviosin 0.67 weight portion, add effervescent acid source citric acid 10 weight portions, alkali source 10 weight portions, and this alkali source is made up of sodium carbonate and sodium bicarbonate.This adds disintegrating agent carboxymethyl base Starch Sodium 16 weight portions, and with the abundant mixing of spray powder, material is dry granulation under 18-60 ℃ of temperature, and granulate gets granule, packing, promptly.
The present invention gives birth to BAIPAO and rises particulate method of quality control, and is specific as follows:
(1) thin layer of Fructus Lycii is differentiated
It is an amount of to get this product, adds water 20ml dissolving, is transferred in the separatory funnel, uses ethyl acetate extraction 2 times, and each 20ml divides and gets ethyl acetate liquid, merges, and water-bath concentrates, and is settled to 1ml with ethyl acetate, as formulation soln.Get Fructus Lycii control medicinal material powder (40 order) 2g, add 60% ethanol 30ml reflux, extract, 30 minutes, filter, filtrate evaporates into does not have the alcohol flavor, is transferred in the separatory funnel water 10ml gradation washing evaporating dish, washing liquid is incorporated in the separatory funnel, with ethyl acetate extraction 2 times, each 20ml divides and gets ethyl acetate liquid, merge, water-bath concentrates, and is settled to 1ml with ethyl acetate, in contrast medical material solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with ethyl acetate-dichloromethane-formic acid (2: 6: 1), be developing solvent, launch, take out, dry.Observe fluorescence at ultraviolet 365nm, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle that same color is arranged.
(2) thin layer of Radix Angelicae Sinensis is differentiated
It is an amount of to get this product, adds 40ml ethyl acetate supersound extraction 20 minutes, filters, and filtrate is put evaporate to dryness in the water-bath, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 0.5g and adds 10ml ethyl acetate supersound extraction 20 minutes, filters, and filtrate is put evaporate to dryness in the water-bath, and residue adds ethyl acetate 2ml makes dissolving, in contrast medical material solution.According to thin layer chromatography (" 2000 editions one appendix VI B of Chinese pharmacopoeia) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel H lamellae, with petroleum ether (60～90 ℃)-ethyl acetate (10: 1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
The said this product of getting is in right amount by 2-5g left and right sides sampling amount.
(3) content Determination of Icariin is measured
With octadecylsilane chemically bonded silica is filler;
Mobile phase is:
Acetonitrile 25 volumes
0.1% trifluoroacetic acid aqueous solution, 75 volumes
Mobile phase can also for
Acetonitrile 25 volumes
0.1% acetic acid (or phosphoric acid) aqueous solution, 75 volumes
The detection wavelength is 270nm;
Number of theoretical plate calculates by the icariin peak should be not less than 3000
(4) content of ferulic acid is measured
With octadecylsilane chemically bonded silica is filler;
Mobile phase is:
Acetonitrile 35 volumes
0.1% trifluoroacetic acid water, 65 volumes
Mobile phase can also for
Acetonitrile 35 volumes
0.1% phosphate aqueous solution, 65 volumes
The detection wavelength is 313nm;
Number of theoretical plate calculates by the icariin peak should be not less than 3000.
(5) content of total flavone is measured
UV spectrophotometer measuring
The detection wavelength is 270nm
With methanol is blank, detects with ultraviolet spectrophotometry.
(specific embodiment)
Embodiment BAIPAO in all one's life is risen particulate preparation
Take by weighing raw material Herba Epimedii 240g, Fructus Psoraleae 120g, Radix Aconiti Lateralis Preparata (system) 80g, Fructus Lycii 240g, Radix Astragali 240g, Caulis Spatholobi 240g, Radix Rubiae 240g, Radix Angelicae Sinensis 120g, Rhizoma Phragmitis 240g, Radix Ophiopogonis 120g, Radix Glycyrrhizae 120g.
More than ten simply, decoct with water secondary, each 1 hour, collecting decoction filters, and filtrate decompression is concentrated into relative density 1.24～1.27 (25 ℃), add ethanol and make and contain alcohol amount and reach 70%, leave standstill, filter, filtrate recycling ethanol is concentrated into relative density 1.10 (50 ℃), adds cosolvent beta-schardinger dextrin-24g, 55 ℃ of insulations, abundant stirring and dissolving, mesh screen filters, spray drying, 170 ℃ of inlet temperature, 80 ℃ of leaving air temps, the gained spray powder adds disintegrating agent carboxymethyl base Starch Sodium 16g, forming agent lactose 21g, correctives steviosin 0.67g, effervescent citric acid 9.5g, sodium bicarbonate 3.1g, sodium carbonate 6.2g, abundant mixing, material is dry granulation under 18-60 ℃ of temperature, granulate, get granule 216g, packing, every bag of 9g promptly gets product.
Embodiment two concentrated solution relative densities are to the influence of drying process with atomizing
The spray drying efficient of medicinal liquid is relevant with the concentration of medicinal liquid, according to following table, with the relative density 1.06～1.13 (50 ℃) of concentrated solution as striking point.
Table 1 concentrated solution relative density is to the influence of drying process with atomizing
| The relative density of concentrated solution | Influence to drying process with atomizing |
| ????＜1.06 ????1.06～1.13 ????＞1.13 | Spray-dried granules is too thin, and the high normal spray drying of energy consumption, uniform particles medicinal liquid thickness, drying time is long, and granule is thicker |
Embodiment three outlet and inlet temperature are to the influence of spray drying powder
The spray drying condition is very important to the reservation and the grain forming of composition.For the benefit of the reservation of effective ingredient and grain forming compare as table 2 inlet temperature, leaving air temp.
Table 2 outlet and inlet temperature is to the influence of spray drying powder
| Inlet temperature (℃) | Leaving air temp (℃) | Ferulic acid retention rate (%) | Icariin retention rate (%) | Water content (%) | To the influence of granulating |
| ????190 ????180 ????180 ????170 ????170 | ????90 ????80 ????70 ????80 ????70 | ????73.2 ????89.5 ????90.6 ????94.7 ????94.9 | ????95.71 ????97.01 ????97.75 ????98.29 ????98.74 | ????3.5 ????4.1 ????4.3 ????4.7 ????5.0 | Relatively poor better fine better |
The result shows, the water content of this preparation semi-finished product fine silt is at 4.0～5.0% o'clock, and directly dry type makes granularity, granule that hardness is suitable; Water content is higher than at 6.0% o'clock, and mobility of particle is relatively poor, adds adjuvant granulation back moisture and is difficult to be controlled in 5%; Water content was less than 4.0% o'clock, and particulate fine powder is many slightly, and yield rate can descend.Consider the retention rate of effective ingredient simultaneously, therefore should control spray-dired inlet temperature is 170-180 ℃, leaving air temp 70-80 ℃.
The selection of embodiment four pelletizing forming adjuvants
Get the medical material of 1 recipe quantity,, get spray powder, be divided into 5 parts, add not commensurability adjuvant, and the adding lactose is adjusted to same weight by prepared.Dry method is made granule, and particulate effervescency is investigated, and the results are shown in Table 3.
Table 3 adjuvant is to the influence of granule mouldability
| Prescription | Carboxymethylstach sodium (g) | Sodium carbonate (g) | Sodium bicarbonate (g) | Citric acid (g) | The result |
| Granule character | |||||
| ??1 ??2 ??3 ??4 ??5 | ????10 ????10 ????10 ????15 ????20 | ????0 ????7 ????6 ????5.6 ????5 | ????10 ????0 ????1.4 ????2.8 ????5.6 | ????8.6 ????8.6 ????8.6 ????8.6 ????8.6 | The fast slightly moderate effervescent speed of effervescent speed of the fast slightly effervescent speed of the slow slightly effervescent speed of effervescent speed is slow slightly |
As can be seen from Table 3, prescription 4 granules that make, effervescent speed is moderate, so select prescription four for use.
Embodiment five beta-schardinger dextrin-quantity research
Because of fat-soluble flavones ingredient is arranged in the preparation,,,, compare test in order to select the optimum condition of beta-schardinger dextrin-consumption to improve the effective ingredient of preparation so add the beta-schardinger dextrin-hydrotropy.
Get the medical material of 4 recipe quantities,, get concentrated solution, be divided into 4 parts, add not commensurability beta-schardinger dextrin-respectively,, granulate again by prepared by prepared, packing (9g/ bag), promptly.
As investigating index, investigate content of total flavone with total flavones, the results are shown in Table 4.
Table 4 beta-schardinger dextrin-consumption and general flavone content be table as a result
The result shows that solubilization-aid effect was undesirable when the beta-schardinger dextrin-consumption was 5g, when increasing to 10g, general flavone content is higher, and when increasing to 24g and 50g again as the beta-schardinger dextrin-consumption, the retention rate difference of index components is very little during with 10g, so selecting the consumption of beta-schardinger dextrin-is 10-50g, the best is 24g.
Therefore, the consumption that adds the cosolvent beta-schardinger dextrin-in the concentrated medicament is 24g.
Embodiment six raw white kalgan lamb skins clothes liquid is risen particulate component content research with living BAIPAO
" raw white kalgan lamb skin clothes liquid " is reached " give birth to BAIPAO rise granule " and carried out the content contrast test of icariin, ferulic acid and total flavones composition, adopt the room temperature test that keeps sample, experimental result sees Table 5.
The component content contrast test of table 5 " raw white kalgan lamb skin clothes liquid " and " give birth to BAIPAO and rise granule "
| Kind | Inspection item | 0 month | 3 months | 6 months | 12 months |
| Raw white kalgan lamb skin clothes liquid is given birth to BAIPAO and is risen granule | Icariin (mg/ props up) ferulic acid (mg/ props up) total flavones (mg/ props up) icariin (mg/ bag) ferulic acid (mg/ bag) total flavones (mg/ bag) | ????78.0 ????1.80 ????236 ????79.2 ????2.82 ????480 | ????74.0 ????1.60 ????225 ????78.9 ????2.80 ????475 | ????70.4 ????1.36 ????213 ????78.8 ????2.79 ????477 | ????68.0 ????0.92 ????205 ????78.9 ????2.80 ????479 |
From the above, giving birth to the stability that BAIPAO rises granule significantly improves than raw white kalgan lamb skin clothes liquid.
The melting of embodiment seven effervescent granules and plain particles relatively
The melting of table 6 effervescent granule and plain particles relatively
| Medicine | Water consumption (ml/ bag) | Water temperature (℃) | Alr mode | Solution time (second) |
| Effervescent granule | ????50 ????200 ????50 ????200 ????50 ????200 ????50 ????200 | 80-100 80-100 25 (room temperature) 25 (room temperature) 80-100 80-100 25 (room temperatures) 25 (room temperature) | Chopsticks stirring chopsticks stirring chopsticks stirring chopsticks stir or not and stir | ????≤10 ????≤10 ????≤10 ????≤10 ????≤10 ????≤10 ????≤10 ????≤10 |
| Plain particles | ????50 ????200 ????50 ????200 ????50 ????200 ????50 | 80-100 80-100 25, (room temperature) 25, (room temperature) 80-100 80-100 25, (room temperature) | Chopsticks stirring chopsticks stirring chopsticks stirring chopsticks stir and or not | ????≥100 ????≥50 ????≥300 ????≥120 ????≥600 ????≥500 ????≥1200 |
200 25 (room temperatures) do not stir 〉=and 1000
As can be seen from Table 6: effervescent granule has greater advantage than plain particles on melting, can obviously reduce water consumption, has improved the dissolubility of medicine, is suitable for patients such as esophageal carcinoma patient to take.
Embodiment eight gives birth to BAIPAO and rises granule by following method quality control ()
Fructus Lycii is differentiated and gets this product 2g, adds water 20ml dissolving, is transferred in the separatory funnel, uses ethyl acetate extraction 2 times, and each 20ml divides and gets ethyl acetate liquid, merges, and water-bath concentrates, and is settled to 1ml with ethyl acetate, as formulation soln.Get Fructus Lycii control medicinal material powder (40 order) 2g, add 60% ethanol 30ml reflux, extract, 30 minutes, filter, filtrate evaporates into does not have the alcohol flavor, is transferred in the separatory funnel water 10ml gradation washing evaporating dish, washing liquid is incorporated in the separatory funnel, with ethyl acetate extraction 2 times, each 20ml divides and gets ethyl acetate liquid, merge, water-bath concentrates, and is settled to 1ml with ethyl acetate, in contrast medical material solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with ethyl acetate-dichloromethane-formic acid (2: 6: 1), be developing solvent, launch, take out, dry.Observe fluorescence at ultraviolet 365nm, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle that same color is arranged.
Embodiment nine gives birth to BAIPAO and rises granule by following method quality control (two)
Radix Angelicae Sinensis is differentiated and is got this product powder 5g, adds 40ml ethyl acetate supersound extraction 20 minutes, filters, and filtrate is put evaporate to dryness in the water-bath, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 0.5g and adds 10ml ethyl acetate supersound extraction 20 minutes, filters, and filtrate is put evaporate to dryness in the water-bath, and residue adds ethyl acetate 2ml makes dissolving, in contrast medical material solution.According to thin layer chromatography (" 2000 editions one appendix VI B of Chinese pharmacopoeia) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel H lamellae, with petroleum ether (60～90 ℃)-ethyl acetate (10: 1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
Embodiment ten gives birth to BAIPAO and rises granule by following method quality control (three)
Content Determination of Icariin is measured:
[assay] measured according to high performance liquid chromatography (61 pages of 2000 editions appendix of Chinese Pharmacopoeia).
System suitability test Waters510 pump, ultraviolet 486 detectors are filler with octadecylsilane chemically bonded silica, acetonitrile: 0.1% trifluoroacetic acid aqueous solution (25: 75) is a mobile phase, flow velocity is 1ml/min; The detection wavelength is 270nm.Theoretical cam curve is calculated by icariin should be not less than 3000.
The icariin reference substance that the preparation precision of reference substance solution takes by weighing in 60 ℃ of drying under reduced pressure to constant weight is an amount of, and accurate the title decides, and makes the solution that every 1ml contains 0.02mg approximately with mobile phase, promptly.
The preparation precision of need testing solution takes by weighing this product 0.1g, puts in the 50ml measuring bottle, and it is an amount of to add 50% methanol solution, and ultrasonic 30 minutes, be cooled to room temperature, use 50% methanol constant volume, shake up, centrifugal 10 minutes (10000rpm) gets supernatant promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
This product contains Herba Epimedii with icariin (C
33H
40O
15) meter, must not be less than the 68mg/ bag.
Embodiment BAIPAO in ten all one's life is risen granule by following method quality control (four)
Content of ferulic acid is measured:
[assay] measured according to high performance liquid chromatography (61 pages of 2000 editions appendix of Chinese Pharmacopoeia).
System suitability test Waters 510 pumps, ultraviolet 486 detectors are filler with octadecylsilane chemically bonded silica, acetonitrile: 0.1% trifluoroacetic acid aqueous solution (35: 65) is a mobile phase, flow velocity is 1ml/min; The detection wavelength is 313nm.Theoretical cam curve is calculated by ferulic acid should be not less than 3000.
Trifluoroacetic acid is changed to glacial acetic acid, obtains same effect.
The ferulic acid reference substance that the preparation precision of reference substance solution takes by weighing in 60 ℃ of drying under reduced pressure to constant weight is an amount of, and accurate the title decides, and makes the solution that every 1ml contains 0.01mg with mobile phase, promptly.
The preparation precision of need testing solution takes by weighing this product 0.5g, puts in the 50ml measuring bottle, and it is an amount of to add 50% methanol solution, and ultrasonic 30 minutes, be cooled to room temperature, use 50% methanol constant volume, shake up, centrifugal 10 minutes (10000rpm) gets supernatant promptly.
Measure accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.
This product contains Radix Angelicae Sinensis with ferulic acid (C
10H
10O
4) meter, must not be less than the 2mg/ bag.
Embodiment 12 gives birth to BAIPAO and rises granule by following method quality control (five)
Content of total flavone is measured:
[assay] measured according to ultraviolet spectrophotometry (33 pages of 2000 editions appendix of Chinese Pharmacopoeia).
With methanol is blank, and the detection wavelength is 270nm.
The icariin reference substance that the preparation precision of reference substance solution takes by weighing in 60 ℃ of drying under reduced pressure to constant weight is an amount of, and accurate the title decides, and makes the solution that every 1ml contains 0.01mg approximately with methanol, promptly.
The preparation of need testing solution takes by weighing polyamide 5g in glass chromatography column (Φ 2cm, long 10cm), and after slowly washing with methanol 50ml, reuse 50ml distilled water wash is standby.Precision takes by weighing this product 0.05g, puts in the 50ml measuring bottle, and the adding distilled water is an amount of, ultrasonic 30 minutes, be cooled to room temperature, use methanol constant volume, shake up, centrifugal 10 minutes (10000rpm), precision is measured supernatant 10ml and is slowly added on the polyamide column, use the 20ml distilled water wash, drip-dry moisture, with methanol-eluted fractions to the 50ml measuring bottle, standardize solution, shake up, as need testing solution.
Algoscopy gets reference substance solution respectively and need testing solution is put in the cuvette in right amount, measures, promptly.
This product contains total flavones with icariin (C
33H
40O
15) meter, must not be less than the 300mg/ bag.
Description of drawings:
Accompanying drawing 1 icariin mark product HPLC figure
Accompanying drawing 2 is given birth to BAIPAO and is risen particulate samples HPLC figure
Accompanying drawing 3 lacks Herba Epimedii negative sample HPLC figure
Accompanying drawing 4 Resina Ferulae acidity scale product HPLC figure
Accompanying drawing 5 is given birth to BAIPAO and is risen particulate samples HPLC figure
Accompanying drawing 6 lacks Radix Angelicae Sinensis negative sample HPLC figure
Claims (10)
1, a kind of granule of promoting leucocytes, by 240 weight portion Herba Epimedii, 120 weight portion Fructus Psoraleaes, 80 weight portion Radix Aconiti Lateralis Preparata, 240 weight portion Fructus Lycii, the 240 weight portion Radixs Astragali, 240 weight portion Caulis Spatholobis, 240 weight portion Radix Rubiaes, 120 weight portion Radix Angelicae Sinensis, 240 weight portion Rhizoma Phragmitiss, 120 weight portion Radix Ophiopogonis, 120 weight portion Radix Glycyrrhizaes are that crude drug is made, it is characterized in that: contain cosolvent beta-schardinger dextrin-10-50 weight portion, contain disintegrating agent carboxymethyl base Starch Sodium 16 weight portions, contain forming agent dextrin 21 weight portions, contain correctives steviosin 0.67 weight portion, contain effervescent 20 weight portions, this effervescent is by citric acid, and sodium carbonate and sodium bicarbonate are formed.
2, the granule of a kind of promoting leucocytes according to claim 1 is characterized in that: contain cosolvent beta-schardinger dextrin-24 weight portions.
3, the preparation method of the granule of a kind of promoting leucocytes according to claim 1 and 2 is as follows by concrete steps:
Take by weighing Herba Epimedii, Fructus Psoraleae, Radix Aconiti Lateralis Preparata, Fructus Lycii, the Radix Astragali, Caulis Spatholobi, Radix Rubiae, Radix Angelicae Sinensis, Rhizoma Phragmitis, Radix Ophiopogonis, Radix Glycyrrhizae, standby;
More than ten simply, decoct with water secondary, each 1 hour, collecting decoction filters, and filtrate decompression is concentrated into 25 ℃ and measures relative density 1.25, add ethanol and make and contain alcohol amount and reach 70%, left standstill 24 hours, filter, filtrate recycling ethanol adds cosolvent beta-schardinger dextrin-10-50 weight portion, and 60 ℃ were stirred 1 hour, be concentrated into 50 ℃ and measure relative density 1.10, filter spray drying, inlet temperature 160-190 ℃, leaving air temp 60-90 ℃, get spray powder; Add-on type agent dextrin 21 weight portions add correctives steviosin 0.67 weight portion, add effervescent, acid source 10 weight portions, and this acid source is made up of citric acid, alkali source 10 weight portions, this alkali source is made up of sodium carbonate and sodium bicarbonate.Add disintegrating agent carboxymethyl base Starch Sodium 16 weight portions, with the abundant mixing of spray powder, material is dry granulation under 18-60 ℃ of temperature, granulate, packing, promptly.
4. the method for quality control of the granule of a kind of promoting leucocytes according to claim 1 and 2 is characterized in that:
Fructus Lycii is differentiated and gets effervescent 2g, adds water 20ml dissolving, is transferred in the separatory funnel, uses ethyl acetate extraction 2 times, and each 20ml divides and gets ethyl acetate liquid, merges, and water-bath concentrates, and is settled to 1ml with ethyl acetate, as formulation soln; Getting granularity is 40 purpose Fructus Lycii control medicinal material powder 2g, adds 60% ethanol 30ml reflux, extract, 30 minutes, filters, filtrate evaporates into does not have the alcohol flavor, is transferred in the separatory funnel water 10ml gradation washing evaporating dish, washing liquid is incorporated in the separatory funnel, with ethyl acetate extraction 2 times, each 20ml divides and gets ethyl acetate liquid, merge, water-bath concentrates, and is settled to 1ml with ethyl acetate, in contrast medical material solution; Draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with volume ratio is that ethyl acetate-dichloromethane-formic acid of 2: 6: 1 is developing solvent, launch, take out, dry, observe fluorescence at ultraviolet 365nm place, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle that same color is arranged; Radix Angelicae Sinensis is differentiated and is got this product powder 5g, adds 40ml ethyl acetate supersound extraction 20 minutes, filters, and filtrate is put evaporate to dryness in the water-bath, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 0.5g and adds 10ml ethyl acetate supersound extraction 20 minutes, filters, and filtrate is put evaporate to dryness in the water-bath, and residue adds ethyl acetate 2ml makes dissolving, in contrast medical material solution; Draw each 10 μ l of above-mentioned two kinds of solution, putting respectively on same silica gel H lamellae, is that petroleum ether-ethyl acetate of 10: 1 is developing solvent with volume ratio, and the boiling spread of petroleum ether is 60～90 ℃, launch, take out, dry, put under the ultra-violet lamp and inspect, wavelength 365nm, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
5. according to the granule of described a kind of promoting leucocytes of claim 1 or 2, its content Determination of Icariin assay method is:
The icariin reference substance that the preparation precision of reference substance solution takes by weighing in 60 ℃ of drying under reduced pressure to constant weight is an amount of, and accurate the title decides, and makes the solution that every 1ml contains 0.02mg with mobile phase, promptly;
The preparation precision of need testing solution takes by weighing this product 0.1g, puts in the 50ml measuring bottle, and it is an amount of to add 50% methanol solution, and ultrasonic 30 minutes, be cooled to room temperature, use 50% methanol constant volume, shake up, centrifugal 10 minutes of 10000rpm gets supernatant promptly;
Chromatographic condition: with octadecylsilane chemically bonded silica is filler
Volume ratio is that 25: 75 acetonitrile-0.1% trifluoroacetic acid water is mobile phase;
The detection wavelength is 270nm
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid.
6. the icariin content assaying method of granule according to claim 5 is characterized in that:
Mobile phase is that volume ratio is 25: 75 acetonitrile-0.1% an acetic acid water;
7. the icariin content assaying method of granule according to claim 5 is characterized in that:
Mobile phase is that volume ratio is 25: 75 acetonitrile-0.1% phosphoric acid water;
8. according to the granule of described a kind of promoting leucocytes of claim 1 or 2, its content of ferulic acid assay method is:
The reference substance solution preparation: the ferulic acid reference substance that precision takes by weighing in 60 ℃ of drying under reduced pressure to constant weight is an amount of, and accurate the title decides, and makes the solution that every 1ml contains 0.01mg with mobile phase, promptly;
Need testing solution preparation: precision takes by weighing this product 0.5g, puts in the 50ml measuring bottle, and it is an amount of to add 50% methanol solution, and ultrasonic 30 minutes, be cooled to room temperature, use 50% methanol constant volume, shake up, centrifugal 10 minutes (10000rpm) gets supernatant promptly;
Chromatographic condition: with octadecylsilane chemically bonded silica is filler,
Volume ratio is that 35: 65 acetonitrile-0.1% sour water is a mobile phase;
The detection wavelength is 313nm
Measure: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid.
9. the ferulaic acid content assay method of granule according to claim 8 is characterized in that:
Mobile phase is that volume ratio is 35: 65 acetonitrile-0.1% phosphoric acid water;
10. according to the granule of described a kind of promoting leucocytes of claim 1 or 2, its content of total flavone assay method is:
The icariin reference substance that the preparation precision of reference substance solution takes by weighing in 60 ℃ of drying under reduced pressure to constant weight is an amount of, and accurate the title decides, and makes the solution that every 1ml contains 0.01mg with methanol, promptly.
The preparation of need testing solution takes by weighing polyamide 5g in glass chromatography column, this column diameter 2cm, and long 10cm, after the slow washing of methanol 50ml, reuse 50ml distilled water wash is standby; Precision takes by weighing this product 0.05g, puts in the 50ml measuring bottle, and the adding distilled water is an amount of, ultrasonic 30 minutes, be cooled to room temperature, use methanol constant volume, shake up, centrifugal 10 minutes of 10000rpm, precision is measured supernatant 10ml and is slowly added on the polyamide column, use the 20ml distilled water wash, drip-dry moisture, with methanol-eluted fractions to the 50ml measuring bottle, standardize solution, shake up, as need testing solution;
UV spectrophotometer measuring
The detection wavelength is 270nm
Algoscopy is blank with methanol, gets reference substance solution respectively and need testing solution is measured.
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| CN (1) | CN1311812C (en) |
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| CN101234181B (en) * | 2008-02-04 | 2011-04-06 | 邵振启 | Medicament for preventing and treating leukopenia used in tumor radiotherapy and chemotherapy course |
| CN101181412B (en) * | 2007-11-21 | 2011-11-23 | 翟慧 | Chinese medicine prescription orally taken for curing leukocytopenia |
| CN102445502A (en) * | 2010-10-14 | 2012-05-09 | 天津天士力之骄药业有限公司 | Method for measuring content of three flavonoids components in ophiopogon root medicinal material |
| CN104198616A (en) * | 2014-09-17 | 2014-12-10 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Method for determining content of icariin in climacterium capsule |
| CN104338031A (en) * | 2014-10-14 | 2015-02-11 | 磐安县道地磐药中药研究所 | Leukocyte-increasing traditional Chinese medicine decoction piece combined preparation as well as preparation method and combined package thereof |
| CN105343608A (en) * | 2015-11-25 | 2016-02-24 | 孙殿亮 | Traditional Chinese medicine preparation for treating leucopenia after chemotherapy and preparation method of traditional Chinese medicine preparation for treating leucopenia after chemotherapy |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101181412B (en) * | 2007-11-21 | 2011-11-23 | 翟慧 | Chinese medicine prescription orally taken for curing leukocytopenia |
| CN101234181B (en) * | 2008-02-04 | 2011-04-06 | 邵振启 | Medicament for preventing and treating leukopenia used in tumor radiotherapy and chemotherapy course |
| CN102445502A (en) * | 2010-10-14 | 2012-05-09 | 天津天士力之骄药业有限公司 | Method for measuring content of three flavonoids components in ophiopogon root medicinal material |
| CN102445502B (en) * | 2010-10-14 | 2014-07-23 | 天津天士力之骄药业有限公司 | Method for measuring content of three flavonoids components in ophiopogon root medicinal material |
| CN104198616A (en) * | 2014-09-17 | 2014-12-10 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Method for determining content of icariin in climacterium capsule |
| CN104338031A (en) * | 2014-10-14 | 2015-02-11 | 磐安县道地磐药中药研究所 | Leukocyte-increasing traditional Chinese medicine decoction piece combined preparation as well as preparation method and combined package thereof |
| CN105343608A (en) * | 2015-11-25 | 2016-02-24 | 孙殿亮 | Traditional Chinese medicine preparation for treating leucopenia after chemotherapy and preparation method of traditional Chinese medicine preparation for treating leucopenia after chemotherapy |
| CN109557192A (en) * | 2018-07-05 | 2019-04-02 | 湖北梦阳药业股份有限公司 | A kind of raw white kalgan lamb skin takes the detection method of liquid |
| CN112014481A (en) * | 2019-05-29 | 2020-12-01 | 湖北梦阳药业股份有限公司 | Detection method of fingerprint spectrum of Shengbai oral liquid |
| CN112007114A (en) * | 2019-05-29 | 2020-12-01 | 湖北梦阳药业股份有限公司 | Medicine for treating leucopenia and preparation method and application thereof |
| WO2020238420A1 (en) * | 2019-05-29 | 2020-12-03 | 湖北梦阳药业股份有限公司 | Drug for treating leukopenia, preparation method therefor and use thereof |
| US20210379138A1 (en) * | 2019-05-29 | 2021-12-09 | Hubei Monyan Pharmaceutical Co., Ltd. | Drug for treating leukopenia, preparation method thereof and use thereof |
| CN112007114B (en) * | 2019-05-29 | 2022-05-13 | 湖北梦阳药业股份有限公司 | Medicine for treating leucopenia and preparation method and application thereof |
| EP3888670A4 (en) * | 2019-05-29 | 2022-06-15 | Hubei Monyan Pharmaceutical Co., Ltd. | Drug for treating leukopenia, preparation method therefor and use thereof |
| AU2020281973B2 (en) * | 2019-05-29 | 2023-07-13 | Hubei Monyan Pharmaceutical Co., Ltd. | Drug for treating leukopenia, preparation method therefor and use thereof |
| US11801280B2 (en) * | 2019-05-29 | 2023-10-31 | Hubei Monyan Pharmaceutical Co., Ltd. | Drug for treating leukopenia, preparation method thereof and use thereof |
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|---|---|
| CN1311812C (en) | 2007-04-25 |
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