CN101439078A - Chinese medicine granule containing astragalus extract and preparation method thereof - Google Patents
Chinese medicine granule containing astragalus extract and preparation method thereof Download PDFInfo
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- CN101439078A CN101439078A CNA2007101503169A CN200710150316A CN101439078A CN 101439078 A CN101439078 A CN 101439078A CN A2007101503169 A CNA2007101503169 A CN A2007101503169A CN 200710150316 A CN200710150316 A CN 200710150316A CN 101439078 A CN101439078 A CN 101439078A
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- extract
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- radix astragali
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- 235000019206 astragalus extract Nutrition 0.000 title abstract 2
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Abstract
The invention provides a traditional Chinese medicine granular preparation with astragalus extract and a preparation method thereof. Traditional Chinese medicine spheroidized particles are prepared by using a traditional Chinese medicine extract and a pharmaceutically acceptable carrier. The shapes of the traditional Chinese medicine spheroidized particles are spherical or similar to spheres, and the density of the traditional Chinese medicine spheroidized particles ranges from 0.6 g/ml to 1.3 g/ml. A single dose of the spheroidized particles is small, the medicine taking is convenient, and the granular preparation can be used as a semifinished product of capsules and can also be used for developing sustained and controlled release preparations of traditional Chinese medicine.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation and preparation method thereof, be specifically related to a kind of Chinese medicinal granule that contains Radix Astragali extract and preparation method thereof.
Background technology
According to China's Epidemiological study, though over nearly 50 years in the rural area or the city, the M ﹠ M of cardiovascular and cerebrovascular disease is all in rising trend.50-60 age China population cause of death central vessel disease and cerebrovascular occupy the five or six respectively, then rise to the two or three respectively later in 1975, and cardiovascular and cerebrovascular disease death person has accounted for first of whole disease cause of the death.China accounts for the percentage ratio of total dead population because of cardiovascular and cerebrovascular disease death person, rise to 42.6% of calendar year 2001 by 12.07% of nineteen fifty-seven, the person reaches 2,000,000 though die from the cardiovascular and cerebrovascular disease every year has the part patient to survive through rescue in addition, but majority stays deformity, can't take care of oneself, cause serious burden to relatives and society.Cardiovascular and cerebrovascular disease also is western countries crowd main causes of death.Infer that according to present existing epidemiologic data advancing of disease trend is: to the year two thousand twenty, the human diseases cause of the death puts in order will have great change, but coronary heart disease and apoplexy will be first and second of the human cause of the death.Till that time, estimate that global coronary heart disease death number will increase to 1,100 ten thousand from 6,300,000 of nineteen ninety; Apoplexy increases to 7,700,000 from 4,400,000.Blood circulation cause of the death formation will increase 59.6% in 30 years, and coronary heart disease and apoplexy increase 74.6% and 75% respectively.These data prove absolutely that cardiovascular and cerebrovascular disease is not only the principal disease of harm humans health, especially human " the No.1 killer " who causes death, disables at present and in following 20 years.
In the medicine of cardiovascular and cerebrovascular disease, the application of Chinese medicine and western medicine emphasizes particularly on different fields, and Chinese medicine also occupies the bigger market share with the little advantage of its side effect.In the Chinese patent medicine of present numerous treatment cardiovascular and cerebrovascular diseases, be that the Chinese patent medicine of main active such as Radix Notoginseng total arasaponins, Radix Salviae Miltiorrhizae total phenolic acids, Radix Puerariae flavone, Herb Gynostemmae Pentaphylli total glycosides etc. more and more is subject to people's attention with effective site.The effect of the various effective ingredient in Chinese of treatment cardiovascular and cerebrovascular disease is had nothing in common with each other and is stressed, and therefore, has the great demand of drug combination clinically.
The traditional preparation process method of Chinese medicinal granule is to adopt dry method or wet method to make the particulate material of certain particle size Chinese medicine or its extract, when using for the patient with mixing in water for oral taking or swallow.The at present common several granule preparation technologies and the defective of existence thereof: 1. conventional particles preparation technology, because Chinese medical concrete viscosity is higher, there are problems such as particulate drug loading is low, outward appearance is not attractive in appearance, mouthfeel is poor, the easy moisture absorption mostly in the preparation method of conventional particles.2. comparatively popular at present fluidized bed granulation technology, be that drug powder and various adjuvant are packed in the container, be blown into the air-flow of preference temperature by sieve plate from the bed bottom, make material mix homogeneously under fluidized state, begin evenly to spray into binder liq then, powder begins coalescent granulating, through spraying and drying repeatedly, when granular size meets the requirements, stop spraying, continue dry.This technology can be reduced to the adjuvant amount more than 50% by traditional 80%, the single dose of the grain products of preparation generally can be reduced to 3g to 5g by traditional 10g, but this technology can not thoroughly solve the problem of viscosity of Chinese medicine extract, used adjuvant can not further reduce, single agent dose is bigger, and patient's compliance is relatively poor; And use this kind method to be not suitable for making solid preparations such as capsule; Adopting the granule of fluidized bed granulation technology preparation at present commonly used in addition is cellular, irregular shape; Moisture absorption is more common, and inconvenience is preserved; Particulate specific surface area is bigger, is not suitable for coating.3. also having Chinese medicine or plant amedica extract is the research of the micropill technology of 700～1500 μ m with fluidized-bed process manufacturing particle diameter, but this technology all is that medicine is made dry powder, water or other mixing material are as binding agent, add medicine dry powder while spraying into liquid adhesive, make micropill.At present the micropill dissolve scattered time limit that adopts this explained hereafter is generally all at 40 minutes, and defective such as production process is comparatively complicated, cost is high, the influence factor is more (for example can not make when air humidity is big), loss is bigger.4. also have to adopt in formulation art and extrude round or extrude the technology that spheronization is made micropill or spheroidal particle, this technology makes the goods support large usage quantity, and drug loading is general below 25%, and dissolve scattered time limit is more than 30 minutes.5. in formulation art, spray or side pressure spray process at the bottom of the fluid bed of employing are also arranged, make Western medicine micropill or spheroidal particle, be used for the exploitation of slow releasing preparation more, so development product generally has slow controlled release characteristics, do not possess the rapid release characteristic.
The rapid release of Chinese medicine and quick acting are importances of the modernization of Chinese medicine, adopt the Chinese medicine of manufacturing of the present invention or plant amedica granule to have fast instant diffusing characteristic.
Summary of the invention
The object of the present invention is to provide a kind of Chinese medicinal granule that contains Radix Astragali extract.
Another object of the present invention is to provide a kind of preparation method that contains the Chinese medicinal granule of Radix Astragali extract.
The Chinese medicinal granule that the present invention contains Radix Astragali extract is achieved through the following technical solutions:
Made by Chinese medicine extract and pharmaceutically acceptable carrier, wherein Chinese medicine extract accounts for 40～90% of percentage by weight, and pharmaceutically acceptable vehicle weight percentage composition is 10～60%; Described Chinese medicine extract is made up of following materials of weight proportions: Radix Salviae Miltiorrhizae extract 5.0%～70.0%, and Radix Notoginseng extract 10.0%～85.0%, Radix Astragali extract 5.0%～70.0% and Borneolum Syntheticum 1.0%～15.0% are standby; Content of danshinolic acid B is at 45%-70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is at 2-10%, and rosmarinic acid contents is at 4%-20%, and alkannic acid content is at 1%-10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%-10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%-6%, and ginsenoside Rg1's content is 15%-40%, and ginsenoside Rb1's content is 15%-40%, ginsenoside Rd's content is 5%-12%, and the content of its Radix Notoginseng total arasaponins is more than 70%; Astragaloside content is 5%-15% in the Radix Astragali extract, and the content of its Radix Astragali total saponins is more than 70%.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, preferably is achieved through the following technical solutions:
Weight percentage by Chinese medicine extract is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%; Wherein said Chinese medicine extract is made up of following materials of weight proportions: Radix Salviae Miltiorrhizae extract 15.0%～50.0%, and Radix Notoginseng extract 25.0%～65.0%, Radix Astragali extract 15.0%～50.0% and Borneolum Syntheticum 2.0%～12.0% are standby; Content of danshinolic acid B is at 45%-70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is at 2-10%, and rosmarinic acid contents is at 4%-20%, and alkannic acid content is at 1%-10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%-10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%-6%, and ginsenoside Rg1's content is 15%-40%, and ginsenoside Rb1's content is 15%-40%, ginsenoside Rd's content is 5%-12%, and the content of its Radix Notoginseng total arasaponins is more than 70%; Astragaloside content is 5%-15% in the Radix Astragali extract, and the content of its Radix Astragali total saponins is more than 70%.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, and the best is achieved through the following technical solutions:
Weight percentage by Chinese medicine extract is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%; Wherein Chinese medicine extract is made up of following materials of weight proportions: Radix Salviae Miltiorrhizae extract 23%, and Radix Notoginseng extract 45%, Radix Astragali extract 23% and Borneolum Syntheticum 9% are standby; Content of danshinolic acid B is at 45%-70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is at 2-10%, and rosmarinic acid contents is at 4%-20%, and alkannic acid content is at 1%-10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%-10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%-6%, and ginsenoside Rg1's content is 15%-40%, and ginsenoside Rb1's content is 15%-40%, ginsenoside Rd's content is 5%-12%, and the content of its Radix Notoginseng total arasaponins is more than 70%; Astragaloside content is 5%-15% in the Radix Astragali extract, and the content of its Radix Astragali total saponins is more than 70%.
Chinese medicine extract described in the present invention, can obtain according to method provided by the invention, also can get as the preparation of methods such as decocting method, infusion process, percolation, circumfluence method, water extract-alcohol precipitation, alcohol extracting-water precipitating according to present technique field routine or commonly used method; Can be extractum, also can be the effective site of further extraction separation acquisition or the compositions of effective site.
Radix Salviae Miltiorrhizae extract in the above-mentioned Chinese medicine composition, can utilize the preparation method of prior art to obtain, for example can utilize Chinese patent application CN1352985A, CN1247855A, CN1242364A, CN1384090A, 02117923.9, (Yunnan University of Traditional Chinese Medicine's journal such as Guo Ying, 2001,24 (4): preparation method 6) obtains.Also can grope preparation technology voluntarily obtains.Content of danshinolic acid B is at 45%-70% in the Radix Salviae Miltiorrhizae extract of the present invention, and salvianolic acid E content is at 2-10%, and rosmarinic acid contents is at 4%-20%, and alkannic acid content is at 1%-10%, and its total phenolic content is preferably in more than 80% more than 70%.No matter be or groping preparation technology voluntarily prepares Radix Salviae Miltiorrhizae extract of the present invention,, then should make with extra care, make it to meet above-mentioned content standard if do not reach above-mentioned content standard by prior art.Its assay and finger printing are as follows:
(1) assay (high performance liquid chromatography) of salvianolic acid B, salvianolic acid E, rosmarinic acid, alkannic acid in the above-mentioned Radix Salviae Miltiorrhizae extract
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Acetonitrile-water-phosphoric acid (23.5:76.5:0.02) is mobile phase; The detection wavelength is 288nm.Number of theoretical plate is pressed the salvianolic acid B peak and is calculated, and should be not less than 5000.
The preparation precision of reference substance solution takes by weighing the salvianolic acid B reference substance, adds mobile phase and makes the solution that every 1ml contains 0.2mg; Salvianolic acid E is made the solution that every 1ml contains 0.02mg; Rosmarinic acid is made the solution that every 1ml contains 0.05mg; Alkannic acid is made the solution that every 1ml contains 0.01mg.
The preparation precision of need testing solution takes by weighing the about 35mg of this product, puts in the 25ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shakes up; Precision is measured 5ml and is put in the 25ml measuring bottle, is diluted to scale with mobile phase, shakes up, 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.
(2) mensuration (spectrophotography) of the total phenolic acid of above-mentioned Radix Salviae Miltiorrhizae extract
The preparation precision of reference substance solution takes by weighing the salvianolic acid B reference substance, makes the solution that every 1ml contains 20 μ g with acetonitrile-water-phosphoric acid (23.5:76.5:0.02) mixed solution, promptly.
The preparation precision of need testing solution takes by weighing the about 25mg of this product, puts in the 50ml measuring bottle, with acetonitrile-water-phosphoric acid (23.5:76.5:0.02) mixed solution dissolving and be diluted to scale, shake up, precision is measured 2ml, puts in the 50ml measuring bottle, add above-mentioned mixed solution and be diluted to scale, shake up, promptly.
Algoscopy is got reference substance solution and need testing solution respectively, is blank with acetonitrile-water-phosphoric acid (23.5:76.5:0.02), according to spectrophotography (1995 editions appendix VA of Chinese Pharmacopoeia), measures trap at 288nm wavelength place, is calculated as follows, promptly.
Total phenolic content (%)=f (A-B)+B
In the formula: f is a correction factor 0.626;
A is that spectrophotometry is the content of total phenolic acid of contrast calculating with the salvianolic acid B;
B is the content of the salvianolic acid B of high effective liquid chromatography for measuring.
(3) above-mentioned Radix Salviae Miltiorrhizae extract HPLC finger printing
Assay method is referring to the assay (high performance liquid chromatography) of salvianolic acid B, salvianolic acid E, rosmarinic acid, alkannic acid in (1) above-mentioned Radix Salviae Miltiorrhizae extract.The record chromatograph time is 60 minutes.
Adopting in the total fingerprint peaks the bigger and metastable total peak salvianolic acid B of peak area as the reference peak, is basic calculation relative retention time and relative peak area with the reference peak.The finger printing of above-mentioned Radix Salviae Miltiorrhizae extract should have 5-7 total peak, is generally 6 total peaks.The relative retention time at 6 total peaks is followed successively by 0.55-0.65 (salvianolic acid E peak), 0.66-0.70 (rosmarinic acid peak), 0.71-0.79 (alkannic acid peak), 1 (salvianolic acid B), 1.03-1.12,1.21-1.30.In the total peak unimodal area account for total peak area greater than 20% have only salvianolic acid B (promptly with reference to the peak), salvianolic acid B peak area (promptly with reference to the peak) accounts for the 57%-87% of total peak area, its relative peak area is 1; Relative retention time is that total peak (the being the rosmarinic acid peak) peak area of 0.66-0.70 accounts for the 3%-18% of total peak area, and its relative peak area is 0.03-0.25.The non-total peak gross area is not more than 10% of total peak area.
Radix Notoginseng extract in the above-mentioned Chinese medicine composition, can utilize the preparation method of prior art to obtain, for example can utilize (foreign medical science plant amedica fascicles such as Chinese patent ZL1095363C, Chinese patent application CN1352985A, Qian Tianxiang, 1997,5), the preparation method of national ministry standard WS3-B-3590-2001 (Z) obtains Radix Notoginseng extract 12 (4)), Tang's light (Chinese patent medicine 1990,12 (8):.Also can grope preparation technology voluntarily and extract Radix Notoginseng extract.Can also directly buy Radix Notoginseng extract from the market, for example content is the Radix Notoginseng total arasaponins (wherein Rb1 〉=30%, Rg1 〉=20%, R1 〉=5%, HPLC measure) of 95% (UV mensuration).Arasaponin R1 content should be 2%-10% in the Radix Notoginseng extract of the present invention, ginsenoside Re's content should be 2%-6%, ginsenoside Rg1's content should be 15%-40%, ginsenoside Rb1's content should be 15%-40%, ginsenoside Rd's content should be 5%-12%, the content of its Radix Notoginseng total arasaponins should be preferably in more than 80% more than 70%.No matter be to buy, do not reach above-mentioned content standard, then should make with extra care, make it to meet above-mentioned content standard as purity by prior art for preparing or market.Its assay and finger printing are as follows:
(1) ginsenoside Re, ginsenoside Rd, arasaponin R1, ginsenoside Rg1, ginsenoside Rb1's assay (high performance liquid chromatography) in the above-mentioned Radix Notoginseng extract
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Column temperature: 40 ℃, flow velocity: 0.7ml/min, the detection wavelength is 203nm; The mobile phase of gradient elution is as follows:
| Time | Water | The second eyeball |
| 0 | 70 | 30 |
| 10 | 70 | 30 |
| 30 | 10 | 90 |
The preparation precision of reference substance solution takes by weighing reference substance, add methanol and make the solution that every 1ml contains the 0.2mg ginsenoside Re respectively, every 1ml contains 0.4mg ginsenoside Rd's solution, every 1ml contains the solution of 0.2mg ginsenoside R1, every 1ml contains the solution of 0.4mg Panax Notoginseng saponin R g1, and every 1ml contains 0.4mg ginsenoside Rb1's solution.
The preparation precision of need testing solution takes by weighing the about 20mg of this product, puts in the 50ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shakes up, 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.Radix Notoginseng extract HPLC finger printing of the present invention.
(2) mensuration of above-mentioned Radix Notoginseng extract total saponins (spectrophotography)
(3) above-mentioned Radix Notoginseng extract HPLC finger printing
Assay method is referring to the assay (high performance liquid chromatography) of ginsenoside Re, ginsenoside Rd, arasaponin R1, ginsenoside Rg1, ginsenoside Rb1 in (1) above-mentioned Radix Notoginseng extract.The record chromatograph time is 30 minutes.
Adopting in the total fingerprint peaks the bigger and metastable total peak ginsenoside Rg1 of peak area as the reference peak, is basic calculation relative retention time and relative peak area with the reference peak.The finger printing of above-mentioned Radix Notoginseng extract should have 9-12 total peak, is generally 11 total peaks.The relative retention time at 11 total peaks is followed successively by 0.77-0.85 (arasaponin R1 peak), (0.87-0.97 ginsenoside Re peak), 1 (the ginsenoside Rg1 peak is promptly with reference to the peak), 2.58-2.67,0.68-2.76,2.77-2.81, (2.82-2.91 ginsenoside Rb1 peak), 2.95-3.03,3.05-3.13, (3.15-3.22 ginsenoside Rd peak), 3.24-3.91.In the total peak unimodal area account for total peak area greater than 20% ginsenoside Rg1 peak and ginsenoside Rb1 peak arranged.Ginsenoside Rg1's peak area (promptly with reference to the peak) accounts for the 20%-35% of total peak area, and its relative peak area is 1; Ginsenoside Rb1's peak area accounts for the 30%-50% of total peak area, and its relative peak area is 0.85-2.50; The arasaponin R1 peak area accounts for the 2%-8% of total peak area, and its relative peak area is 0.06-0.40; Ginsenoside Rd's peak area accounts for the 5%-14% of total peak area, and its relative peak area is 0.14-0.70.The non-total peak gross area is not more than 10% of total peak area.
Borneolum Syntheticum in the above-mentioned Chinese medicine composition is artificial Borneolum Syntheticum or natural Broneolum Syntheticum.
Lignum Dalbergiae Odoriferae oil in the above-mentioned Chinese medicine composition is that Lignum Dalbergiae Odoriferae is through the distillation gained.
Pharmaceutically acceptable carrier of the present invention can be any preparation Chinese medicinal granule pharmaceutically acceptable carrier commonly used or conventional, and for example: diluent (filler) includes but not limited to sucrose, dextrin, starch, lactose, mannitol, xylitol, chitosan, SHUANGQITANG, soluble starch, Pulvis Talci or water solublity dextrin etc.; Disintegrating agent includes but not limited to starch, sodium carboxymethyl cellulose (CMS-Na), microcrystalline Cellulose (MCC), micropowder silica gel, hydroxypropyl starch, soluble starch, water solublity dextrin; Inclusion agents includes but not limited to alpha-cyclodextrin (α-CD), beta-schardinger dextrin-(β-CD) and N-LOK modified starch etc.; Wetting agent (binding agent) includes but not limited to water, ethanol, polyvinylpyrrolidone (polyvidone), hydroxypropyl cellulose, Polyethylene Glycol above-mentioned adjuvant function such as diluent such as (PEG), disintegrating agent, wetting agent is called by function in this patent, be viscosity modifier, preferably microcrystalline cellulose (MCC), micropowder silica gel, Polyethylene Glycol, Pulvis Talci, chitosan, Pulvis Talci, the above-mentioned pharmaceutically acceptable carrier of polyvidone can use separately, also can unite use.Persons of ordinary skill in the art may appreciate that the following emerging pharmaceutically acceptable carrier that can be used for preparing Chinese medicinal granule,, also should be included in protection scope of the present invention if can realize purpose of the present invention.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, and described pharmaceutically acceptable carrier preferably one or more in sucrose, dextrin, starch, lactose, mannitol, xylitol, chitosan, SHUANGQITANG, soluble starch, Pulvis Talci, water solublity dextrin sodium carboxymethyl cellulose (CMS-Na), microcrystalline Cellulose (MCC), micropowder silica gel, hydroxypropyl starch, ethanol, hydroxypropyl cellulose, Polyethylene Glycol, chitosan, polyvidone is united use.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, and described pharmaceutically acceptable carrier is preferably: crystalline cellulose element, micropowder silica gel, Polyethylene Glycol, Pulvis Talci, chitosan, Pulvis Talci, polyvidone.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, described granule comprises master batch and the shell that is positioned on the master batch, and profile is sphere or class sphere, and bulk density is 0.6～1.3g/m, dissolve scattered time limit is 0.4～5 minute, and active constituents of medicine is included among master batch and/or the shell.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, and its particle diameter is 700～1500 μ m.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, and described granule also contains coating, and the weight of coating materials accounts for 2～5wt% of granule gross weight.
The Chinese medicinal granule that the present invention contains Radix Astragali extract adopts the fluidized bed granulation technology to granulate, common fluidized bed granulation technology is directly packed into powdered substance and is granulated as bed material in the container of fluid bed, and the present invention forms with pharmaceutically acceptable preparing carriers, perhaps is prepared from by pharmaceutically acceptable carrier and corresponding Chinese medicine extract dry powder.
The present invention contains the preparation method of the Chinese medicinal granule of Radix Astragali extract, and step is as follows:
(1) preparation of active component of the present invention: Radix Salviae Miltiorrhizae extract 5.0%～70.0%, Radix Notoginseng extract 10.0%～85.0%, Radix Astragali extract 5.0%～70.0% and Borneolum Syntheticum 1.0%～15.0%, mix homogeneously, preparation cost invention active component;
(2) preparation of master batch: i. gets an amount of pharmaceutically acceptable carrier, the perhaps mixture of itself and Chinese medicine extract dry powder, and crushing screening obtains the satisfactory material of granularity; Ii. get the material of a part of step I, drop in spray of fluid bed side or the end spray pot, other gets it filled and learns acceptable carrier and/or Chinese medicine extract and add water and be mixed with slurry, adopt spray of fluid bed side or end pressure spray process to spray into, and sift out granule, again parent nucleus is dropped in the pot as parent nucleus, continue to spray and state slurry, the material of remaining step I is sprinkled into fine powder in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, filter out the satisfactory master batch of particle diameter;
(3) preparation of product: it is an amount of to get master batch, and acceptable carrier is an amount of, and active component of the present invention is an amount of; Above-mentioned acceptable carrier is added in the invention described above active component, and it is standby as slurry to mix into suspension; Above-mentioned master batch is dropped in the fluid bed side spray pot, and above-mentioned slurry slowly sprays into, and all sprays into to slurry, makes spheroidal particle.
The present invention contains the preparation method of the Chinese medicinal granule of Radix Astragali extract, and preferred steps is as follows:
(1) preparation of active component of the present invention: get Radix Salviae Miltiorrhizae extract 23%, Radix Notoginseng extract 45%, Radix Astragali extract 23% and Borneolum Syntheticum 9%, mix homogeneously, preparation cost invention active component;
(2) preparation of master batch: the mixture of getting dextrin and starch weight ratio and be 1:1 is crossed 200 mesh sieves, and wherein 60-65wt% drops in the fluid bed side spray pot as bed material; 10-15wt% dextrin and starch mixture, amount to the active component of the present invention that accounts for the 15wt% of master batch weight after the dry weight, adding water is mixed with slurry and sprays into, and to sift out particle diameter be that 180～250 μ m granules are as parent nucleus, again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle dextrin of surplus and the fine powder of starch mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, the master batch that filters out particle diameter and be 450～600 μ m is standby;
(3) preparation of product: get master batch 450g, the active component of the present invention of 230g, with the active component weight ratio of the present invention polyethylene glycol 6000 that is 18:25, perhaps with active component weight ratio of the present invention be 7:25 HPMC and PVP-K30 mixture, wherein the HPMC:PVP-K30 weight ratio is 2:5; With dehydrated alcohol above-mentioned viscosity is adjusted and a kind ofly in agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture to be formulated as the solution that concentration is 15wt%, add in the active component of the present invention, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
The present invention contains in the preparation method of Chinese medicinal granule of Radix Astragali extract, and the temperature of charge of the spheroidal particle that said method can be obtained is controlled at 37～45 ℃; Transparent coating material water is made into the coating solution of 7.5% (g/ml) again, according to the amount of theory weightening finish 3wt% coating solution is sprayed into coating, make spheroidal particle, its bulk density is 0.76g/ml, and dissolve scattered time limit is 25～180 seconds.
The present invention contains in the preparation method of Chinese medicinal granule of Radix Astragali extract, No. 2 capsules of spheroidal particle fill that said method can be obtained, and the 250mg/ grain is made 10000 of capsules.
" setting of dosage form in the Chinese pharmacopoeia, and in order to distinguish different with technology such as micropill, microcapsules in conjunction with the characteristic of present technique preparing product, was named above-mentioned granule and is spheroidized particle according to version in 2005.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, outside it coating can also be arranged, and the weight of coating materials accounts for the 2-5% of granule gross weight.During the spheroidized particle coating, obviously low (plain particles coating, coating materials consumption are 20-30% to the more common granule coating of the consumption of coating materials, and spheroidized particle coating materials consumption then can be reduced to 2-5% with the adjuvant amount.As required, coating can be common film coating, also can be enteric film coating, slow controlled release coat etc., and coating materials can be the commonly used or conventional coating materials in any this area, select according to different needs, the coating process can be carried out according to the method for this area routine.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, directly uses except can be used as common granule, can also be as intermediate, be prepared into dosage forms such as capsule, as granule use etc., can be prepared into sustained-release preparation in addition, positioning release medicine preparation etc.
The present invention contains the Chinese medicinal granule of Radix Astragali extract, and preferred described granule is made conventional capsule agent or sustained-release preparation.
Spheroidized particle of the present invention has the following advantages:
1. the consumption of adjuvant is few, therefore causes single dose little, and the general each dose of patient is that 0.1～4g gets final product, and can reduce the fear that the patient takes medicine and produced heavy dose.
2. outward appearance is good, and granule of the present invention is spherical in shape or class is spherical, the smooth surface rounding, the control of suitable product design quality.
3. physical characteristic is good, and in the spheroidal particle preparation process, mobility of particle is good, causes that particle size distribution is regular, the fine and close anti-extruding of quality, and wear-resistant, density is big, and (bulk density is 0.6～1.3g/ml), specific surface area is little (has only 0.01～0.03m
2/ g).
4. dissolve scattered time limit is short, and the spheroidal particle dissolve scattered time limit of the present invention that adopts this type of prescription to make is short, is generally 0.4～5 minute.
5. granularity test: according to 2000 editions pharmacopeia regulations, get granule 5 bags of (bottle) or multiple dose packing granule 1 bags (bottle) of single dose packing, claim to decide weight, put in the medicine sieve and sieve.When sieving, will sieve and keep level, about come and go and sieved gently 3 minutes.Can not and can must not cross 8.0% by a sieve by the granule and the powder summation of No. four sieves.Granule of the present invention can not and can meet the pharmacopeia regulation by the granule and the powder summation of No. four sieves by a sieve, and its numerical value is no more than 5.5%.
6. melting test: according to 2000 editions pharmacopeia regulations, get medicinal granule test sample 10g of the present invention, add 20 times of hot water, stirred 5 minutes, observe immediately.Soluble granule is answered off-bottom.
These characteristics can improve patient's the row of complying with, and makes the application of packaging technique become possibility, thereby has solved the moisture absorption (critical wettability is promoted to 85% by 60% of plain particles) of Chinese medicine, problem such as stable; In addition, spheroidized particle of the present invention uses except can be used as common granule, can also be as intermediate or granule, and fill becomes dosage forms such as capsule, can be prepared into sustained-release preparation in addition, positioning release medicine preparation etc.
The specific embodiment
The present invention is further illustrated below in conjunction with specific embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
The preparation of active component of the present invention:
Radix Salviae Miltiorrhizae extract: the preparation method by Chinese patent application (application number 02117923.9) obtains.Concrete extracting method is: Radix Salviae Miltiorrhizae 5kg is ground into coarse powder, adds deionized water heating extraction 3 times under 100 ℃ of slight boiling conditions.5.5 times of water heated 1 hour for the first time; Second and third time respectively adds 3 times of water gagings and heated respectively 0.5 hour.Extracting solution filters after transferring pH value to be 2 with 10% hydrochloric acid, polyamide column on the filtrate (dried resin amount make a living dose 2/3).With the washing of 5 times of amount deionizations, continue with 0.1% sodium bicarbonate aqueous solution eluting, consumption is 5 times of column volume.Collect eluent, transfer PH to 2 back to go up D with 10% hydrochloric acid
101Macroporous adsorbent resin, continues to use 95% ethanol elution to neutral with deionized water rinsing, treats that colour band gets off promptly to collect this colour band.Concentrating under reduced pressure is collected liquid to doing to the greatest extent, spend the night with suitable quantity of water dissolving back refrigerator cold-storage, promptly get the Radix Salviae Miltiorrhizae total phenolic acids extracting solution by 0.3 μ m cellulose mixture filtering with microporous membrane, with lyophilization immediately behind the 2% sodium hydroxide adjusting pH value to 6.0, Radix Salviae Miltiorrhizae extract raw material lyophilized powder 221g, product yield 4.4% of the dose of making a living;
Buy Radix Notoginseng total arasaponins from market,, get Radix Notoginseng extract through further refining.The ginsenoside Re is 3.9% in the Radix Notoginseng extract, and the ginsenoside Rg1 is 34.3%, and the ginsenoside Rb1 is 31.0%, and the ginsenoside Rd is 8.8%, and arasaponin R1 is 6.8%, and its content of the total saponins in radix notoginseng is 94%;
Buy Radix Astragali extract from market,, get Radix Astragali extract through further refining.Astragaloside content is 9.5% in the Radix Astragali extract, and the content of Radix Astragali extract is 88.9%;
Get above-mentioned Radix Salviae Miltiorrhizae extract 750g, above-mentioned Radix Notoginseng extract 1500g, above-mentioned Radix Astragali extract 750g, Borneolum Syntheticum 300g, mix homogeneously, preparation cost invention active component;
The preparation of master batch: the weight ratio of getting dextrin and starch is crossed 200 mesh sieves for the 1:1 mixture, wherein 65% as in the bed material input fluid bed side spray pot, other gets starch and adds water and be mixed with starch slurry (15%) and spray into as slurry, and sift out granule (particle diameter is 180-250 μ) as parent nucleus, again parent nucleus is dropped in the pot, continue the spray starch slurry, 35% the dextrin of remainder and the fine powder of starch are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, and it is standby at the master batch of 450 μ-600 μ to filter out particle diameter.
The preparation of product: get master batch 450g, microcrystalline Cellulose (200 order) 50g, polyethylene glycol 6000 (heating and melting)
500G, active component 3200g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and adding water, to mix into solid content be 30% binding agent; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly being dried to simultaneously slurry all sprays into and makes spheroidal particle, temperature of charge is controlled at 55 degrees centigrade, the coating material OPAGLOS2 water that reuse is transparent is made into 7.5% coating solution, amount according to theory weightening finish 3% sprays into coating with coating solution, makes spheroidal particle.Bulk density is 0.76g/ml.With No. 2 capsules of spheroidal particle fill that obtain, every dress 0.125g makes 10000 of capsules.
Embodiment 2
The preparation of active component of the present invention: get Radix Notoginseng extract 2000g, embodiment one Radix Astragali extract 750g, the Borneolum Syntheticum 300g of Radix Salviae Miltiorrhizae extract 1000g, the embodiment one of embodiment one, mix homogeneously, preparation cost invention active component;
The preparation of master batch: the mixture of getting micropowder silica gel and chitosan weight ratio and be 1:1 is crossed 200 mesh sieves, wherein 65% as in the bed material input fluid bed side spray pot, other gets PVP K30 and adds water, extract, is mixed with bonding agent-spray into as slurry, and to sift out particle diameter be that 120-180 μ granule is as parent nucleus, again parent nucleus is dropped in the pot, continue the spray starch slurry, 35% the micropowder silica gel of remainder and the fine powder of chitosan are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, and it is standby at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 300g, microcrystalline Cellulose (200 order) 250g, micropowder silica gel 14g, active component 2000g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and it is standby as slurry to mix into uniform suspension; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly be dried to simultaneously slurry and all spray into and make spheroidal particle, coating material OPAGLOS 2 waters that reuse is transparent are made into 7.5% coating solution, amount according to theory weightening finish 3% sprays into coating with coating solution, makes spheroidal particle.Particulate bulk density 0.93g/ml, with No. 00 capsule of spheroidal particle fill that obtains, every dress 0.70g makes 10000 of capsules.
Embodiment 3
The preparation of active component of the present invention: get Radix Astragali extract 700g, the Borneolum Syntheticum 280g of Radix Notoginseng extract 1360g, embodiment one of Radix Salviae Miltiorrhizae extract 960g, the embodiment one of embodiment one, mix homogeneously is prepared into.
The preparation of master batch: the mixture of getting dextrin and starch weight ratio and be 1:1 is crossed 200 mesh sieves, wherein 65% as in the bed material input fluid bed side spray pot, other gets starch, extract (account for after giving money as a gift master batch weight 15%) and adds water and be mixed with slurry and spray into, and sift out granule (particle diameter is 180～250 μ) as parent nucleus, again parent nucleus is dropped in the pot, continue the spray starch slurry, 35% the dextrin of remainder and the fine powder of starch are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, and it is standby at the master batch of 300 μ～400 μ to filter out particle diameter.
The preparation of product: get master batch 450g, microcrystalline Cellulose (200 order) 50g, polyethylene glycol 6000 (heating and melting)
500G, active component 1000g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and adding water, to mix into solid content be 30% binding agent; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly being dried to simultaneously slurry all sprays into and makes spheroidal particle, temperature of charge is controlled at 55 degrees centigrade, the coating material OPAGLOS2 water that reuse is transparent is made into 7.5% coating solution, amount according to theory weightening finish 3% sprays into coating with coating solution, makes spheroidal particle, and bulk density is 0.76g/ml; With No. 2 capsules of spheroidal particle fill that obtain, every dress 0.125g makes 10000 of capsules.
Embodiment 4
The preparation of active component of the present invention: get Radix Astragali extract 900g, the Borneolum Syntheticum 200g of Radix Notoginseng extract 1500g, embodiment one of Radix Salviae Miltiorrhizae extract 700g, the embodiment one of embodiment one, mix homogeneously.
The preparation of master batch: the mixture of getting dextrin and microcrystalline Cellulose weight ratio and be 1:1 is crossed 200 mesh sieves, wherein 65% as in the bed material input fluid bed side spray pot, other gets PVP K30 and adds water and be mixed with bonding agent (5%) and spray into as slurry, and to sift out particle diameter be that 180～250 μ granules are as parent nucleus, again parent nucleus is dropped in the pot, continue the spray starch slurry, 35% the dextrin of remainder and the fine powder of microcrystalline Cellulose are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, and it is standby at the master batch of 300 μ～400 μ to filter out particle diameter.
The preparation of product: get master batch 1000g, in 5% the polyvidone solution, add active component of the present invention an amount of (being equivalent to 20 kilograms of medical materials); In 5% the polyvidone solution, add that active component of the present invention is an amount of, adding water, to mix into solid content be that 30% suspension is standby as slurry; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly be dried to simultaneously slurry and all spray into and make spheroidal particle, coating material OPAGLOS 2 waters that reuse is transparent are made into 7.5% coating solution, amount according to theory weightening finish 3% sprays into coating with coating solution, makes spheroidal particle.
Embodiment 5
The preparation of active component of the present invention: get Radix Astragali extract 820g, the Borneolum Syntheticum 380g of Radix Notoginseng extract 1350g, embodiment one of Radix Salviae Miltiorrhizae extract 750g, the embodiment one of embodiment one, mix homogeneously, preparation cost invention active component.
The preparation of master batch: the mixture of getting dextrin and microcrystalline Cellulose weight ratio and be 2:1 is crossed 100 mesh sieves, wherein 75% as in the bed material input fluid bed side spray pot, other gets PVP K30 and adds water, extract, is mixed with bonding agent-spray into as slurry, and to sift out particle diameter be that 100-200 μ granule is as parent nucleus, again parent nucleus is dropped in the pot, continue the spray starch slurry, 35% the dextrin of remainder and the fine powder of microcrystalline Cellulose are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, and it is standby at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 800g, microcrystalline Cellulose 190g, micropowder silica gel 35g, active component 2500g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and it is standby as slurry to mix into uniform suspension; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
Embodiment 6
The composition of active component of the present invention: get Radix Astragali extract 170g, the Borneolum Syntheticum 80g of Radix Notoginseng extract 750g, embodiment one of Radix Salviae Miltiorrhizae extract 2300g, the embodiment one of embodiment one, mix homogeneously, preparation cost invention active component.
The preparation of master batch: the mixture of getting micropowder silica gel and Pulvis Talci weight ratio and be 1:1 is crossed 200 mesh sieves, wherein 50% as in the bed material input fluid bed side spray pot, other gets PVP K30 and adds water, extract, is mixed with bonding agent-spray into as slurry, and to sift out particle diameter be that 120-180 μ granule is as parent nucleus, again parent nucleus is dropped in the pot, continue the spray starch slurry, 35% micropowder silica gel and talcous fine powder of remainder is sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, and it is standby at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 300g, microcrystalline Cellulose (200 order) 250g, micropowder silica gel 14g, active component 2000g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and it is standby as slurry to mix into uniform suspension; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
Embodiment 7
The preparation of active component of the present invention: get Radix Astragali extract 2300g, the Borneolum Syntheticum 130g of Radix Notoginseng extract 700g, embodiment one of Radix Salviae Miltiorrhizae extract 170g, the embodiment one of embodiment one, mix homogeneously, preparation cost invention active component.
The preparation of master batch: taking polyethylene glycol and chitosan weight ratio are that the mixture of 1:1 is crossed 200 mesh sieves, wherein 65% as in the bed material input fluid bed side spray pot, other gets PVP K30 and adds water, extract, is mixed with bonding agent-spray into as slurry, and to sift out particle diameter be that 120-180 μ granule is as parent nucleus, again parent nucleus is dropped in the pot, continue the spray starch slurry, 35% the Polyethylene Glycol of remainder and the fine powder of chitosan are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, and it is standby at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 700g, microcrystalline Cellulose (200 order) 300g, micropowder silica gel 20g, active component 1500g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and it is standby as slurry to mix into uniform suspension; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
Embodiment 8:
1, the preparation of active component of the present invention
Get Radix Astragali extract 960g, the Borneolum Syntheticum 250g of Radix Notoginseng extract 1350g, embodiment one of Radix Salviae Miltiorrhizae extract 750g, the embodiment one of embodiment one, mix homogeneously is made active component of the present invention.
2, the preparation of master batch
Get dextrin and starch (1:1) mixture and cross 200 mesh sieves, wherein 65wt% drops in the fluid bed side spray pot, other gets starch and adds water and be mixed with starch slurry (15%, g/ml) spray into as slurry, and sift out granule (particle diameter is 180～250 μ m) as parent nucleus, again parent nucleus is dropped in the pot, continue to spray and state starch slurry, remaining 35% the dextrin and the fine powder of starch (1:1) mixture are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, and it is standby at the master batch of 450～600 μ m to filter out particle diameter.
3, viscosity is adjusted the selection of agent
A. get the invention described above active component, be diluted to the diluent that viscosity is 6.0～9.8MpaS with the alcoholic solution of 60% (ml/ml).
B. get 1 above-mentioned diluent, drop on the microscope slide, hang, solid cicatrix surface, liquid evaporation back does not have complete film, and viscosity is less, easily scrapes with powdery, and it is serious to play powder.
C. the viscosity according to cicatrix among the b is little, film property is poor, intensity is little, easily play characteristics such as powder, select viscosity to adjust agent, experiment shows can select HPMC:PVP-K30 (2:5) mixture to adjust agent as viscosity, and also can select polyethylene glycol 6000 is that viscosity is adjusted agent.
D. HPMC:PVP-K30 (2:5) mixture that to select with active component weight ratio of the present invention be 7:25 is that viscosity is adjusted agent, the polyethylene glycol 6000 that perhaps to select with active component weight ratio of the present invention be 18:25 is that viscosity is adjusted agent, and material viscosity is increased to 16MPaS by 9.0MPaS.
4, the preparation of spheroidal particle of the present invention
A. get master batch 450g, with the active component weight ratio of the present invention polyethylene glycol 6000 that is 18:25, perhaps with active component weight ratio of the present invention be 7:25 HPMC:PVP-K30 (2:5) mixture, the active component of the present invention of 10000g;
B. with dehydrated alcohol above-mentioned viscosity is adjusted and a kind ofly in the agent be formulated as the solution that concentration is 15wt%, add in the active component of the present invention, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry;
C. master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly being dried to simultaneously slurry all sprays into and makes spheroidal particle, temperature of charge is controlled at 37～45 ℃, again transparent coating material water is made into the coating solution of 7.5% (g/ml), coating solution is sprayed into coating, make spheroidal particle according to the amount of theory weightening finish 3wt%, its bulk density is 0.76g/ml, and dissolve scattered time limit is 25 seconds.
With No. 2 capsules of spheroidal particle fill that obtain among the step c, the 250mg/ grain is made capsule.
Embodiment 9
1, the preparation of active component of the present invention: the Radix Astragali extract 670g, the Borneolum Syntheticum 160g that get Radix Notoginseng extract 1800g, the embodiment one of Radix Salviae Miltiorrhizae extract 670g (Chinese patent CN1352985A embodiment 1), embodiment one, mix homogeneously, preparation cost invention active component.
2, the preparation of master batch: get xylitol and carboxymethyl starch sodium (1:1) mixture and cross 200 mesh sieves, wherein 60wt% drops in the fluid bed side spray pot, other gets 10wt% xylitol and carboxymethyl starch sodium (1:1) mixture and active component of the present invention (after amounting to dry weight, account for the 15wt% of master batch weight) add water and be mixed with slurry and spray into, and sift out granule (particle diameter is 180～250 μ m) as parent nucleus, again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle, the xylitol of remaining 30wt% and the fine powder of carboxymethyl starch sodium (1:1) mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, and the master batch that filters out particle diameter and be 280～450 μ m is standby.
3, the preparation of product: get master batch 450g, the active component of the present invention of 2400g, with the active component weight ratio of the present invention polyethylene glycol 6000 that is 18:25, with dehydrated alcohol above-mentioned viscosity is adjusted the agent polyethylene glycol 6000 and be formulated as the solution that concentration is 15wt%, add in the active component of the present invention, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
Embodiment 10
1, the preparation of active component of the present invention: (water is carried 75% alcohol deposition method preparation: Guo Ying etc. to get Radix Salviae Miltiorrhizae extract 500g, Yunnan University of Traditional Chinese Medicine's journal, 2001,6), Radix Notoginseng extract 2100g (Qian Tianxiang etc. 24 (4):, foreign medical science plant amedica fascicle, 1997,12 (4)), Radix Astragali extract 500g, the Borneolum Syntheticum 200g of embodiment one, with the above-mentioned substance mix homogeneously, make active component of the present invention.
2, the preparation of master batch: get lactose and hydroxypropyl starch (1:1) mixture and cross 200 mesh sieves, wherein 60wt% drops in the fluid bed side spray pot, other gets 10wt% lactose and hydroxypropyl starch (1:1) mixture and active component of the present invention (after amounting to dry weight, account for the 15wt% of master batch weight) add water and be mixed with slurry and spray into, and sift out granule (particle diameter is 180～250 μ m) as parent nucleus, again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle, the lactose of remaining 30wt% and the fine powder of hydroxypropyl starch (1:1) mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, and the master batch that filters out particle diameter and be 180～250 μ m is standby.
3, the preparation of product: get master batch 850g, the active component of the present invention of 1500g, with HPMC and PVP-K30 mixture that active component weight ratio of the present invention is 7:25, wherein the HPMC:PVP-K30 weight ratio is 2:5; Above-mentioned viscosity is adjusted agent HPMC and the PVP-K30 mixture is formulated as the solution that concentration is 15wt% with dehydrated alcohol, add in the active component of the present invention, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 20wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
Embodiment 11
1, the preparation of active component of the present invention: get Radix Salviae Miltiorrhizae extract 600g (Chinese patent CN1384090A embodiment 1), Radix Notoginseng extract 800g (Tang's light, Chinese patent medicine, 1990,5), Radix Astragali extract 1650g, the Borneolum Syntheticum 250g of embodiment one 12 (8):, with the above-mentioned substance mix homogeneously, make active component of the present invention.
2, the preparation of master batch: get dextrin and mannitol (3:1) mixture and cross 200 mesh sieves, wherein 64wt% drops in the fluid bed side spray pot, other gets 16wt% dextrin and mannitol mixture and active component of the present invention (after amounting to dry weight, account for the 10wt% of master batch weight) add water and be mixed with slurry and spray into, and sift out granule (particle diameter is 180～250 μ m) as parent nucleus, again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle, the dextrin of remaining 20wt% and the fine powder of mannitol mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, and the master batch that filters out particle diameter and be 450～600 μ m is standby.
3, the preparation of product: get master batch 500g, 1500 active component of the present invention, with HPMC and PVP-K30 mixture that active component weight ratio of the present invention is 7:25, wherein the HPMC:PVP-K30 weight ratio is 2:5; Above-mentioned viscosity is adjusted agent HPMC and the PVP-K30 mixture is formulated as the solution that concentration is 15wt% with dehydrated alcohol, add in the active component of the present invention, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 20wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
Embodiment 12
1, the preparation of active component of the present invention: the Radix Notoginseng extract 1350g, the Radix Astragali extract 800g (Teng Xinglong etc. that get Radix Salviae Miltiorrhizae extract 850g (Chinese patent CN1384090A embodiment 1), embodiment one, Heilungkiang medicine, 2002,340), Borneolum Syntheticum 300g 15 (5):, with the above-mentioned substance mix homogeneously, make active component of the present invention.
2, the preparation of master batch: get dextrin and mannitol (2:1) mixture and cross 200 mesh sieves, wherein 65wt% drops in the fluid bed side spray pot, other gets 25wt% dextrin and mannitol mixture and active component of the present invention (after amounting to dry weight, account for the 10wt% of master batch weight) add water and be mixed with slurry and spray into, and sift out granule (particle diameter is 180～250 μ m) as parent nucleus, again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle, the dextrin of remaining 10wt% and the fine powder of mannitol mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, and the master batch that filters out particle diameter and be 450～600 μ m is standby.
3, the preparation of product: get master batch 450g, the active component of the present invention of 2000g, with the active component weight ratio of the present invention polyethylene glycol 6000 that is 18:25, with dehydrated alcohol above-mentioned viscosity is adjusted the agent polyethylene glycol 6000 and be formulated as the solution that concentration is 15wt%, add in the active component of the present invention, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
Claims (10)
1. a Chinese medicinal granule that contains Radix Astragali extract is made by Chinese medicine extract and pharmaceutically acceptable carrier, it is characterized in that Chinese medicine extract accounts for 40～90% of percentage by weight, and pharmaceutically acceptable vehicle weight percentage composition is 10～60%; Wherein said Chinese medicine extract is made up of following materials of weight proportions: Radix Salviae Miltiorrhizae extract 5.0%～70.0%, and Radix Notoginseng extract 10.0%～85.0%, Radix Astragali extract 5.0%～70.0% and Borneolum Syntheticum 1.0%～15.0% are standby; Content of danshinolic acid B is at 45%-70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is at 2-10%, and rosmarinic acid contents is at 4%-20%, and alkannic acid content is at 1%-10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%-10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%-6%, and ginsenoside Rg1's content is 15%-40%, and ginsenoside Rb1's content is 15%-40%, ginsenoside Rd's content is 5%-12%, and the content of its Radix Notoginseng total arasaponins is more than 70%; Astragaloside content is 5%-15% in the Radix Astragali extract, and the content of its Radix Astragali total saponins is more than 70%.
2. the Chinese medicinal granule that contains Radix Astragali extract according to claim 1, the weight percentage that it is characterized in that Chinese medicine extract is 70～80%, pharmaceutically acceptable vehicle weight percentage composition is 20～30%; Wherein said Chinese medicine extract is made up of following materials of weight proportions: Radix Salviae Miltiorrhizae extract 15.0%～50.0%, and Radix Notoginseng extract 25.0%～65.0%, Radix Astragali extract 15.0%～50.0% and Borneolum Syntheticum 2.0%～12.0% are standby; Content of danshinolic acid B is at 45%-70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is at 2-10%, and rosmarinic acid contents is at 4%-20%, and alkannic acid content is at 1%-10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%-10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%-6%, and ginsenoside Rg1's content is 15%-40%, and ginsenoside Rb1's content is 15%-40%, ginsenoside Rd's content is 5%-12%, and the content of its Radix Notoginseng total arasaponins is more than 70%; Astragaloside content is 5%-15% in the Radix Astragali extract, and the content of its Radix Astragali total saponins is more than 70%.
3. as containing the Chinese medicinal granule of Radix Astragali extract as described in the claim 2, the weight percentage that it is characterized in that Chinese medicine extract is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%; Wherein Chinese medicine extract is made up of following materials of weight proportions: Radix Salviae Miltiorrhizae extract 23%, and Radix Notoginseng extract 45%, Radix Astragali extract 23% and Borneolum Syntheticum 9% are standby; Content of danshinolic acid B is at 45%-70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is at 2-10%, and rosmarinic acid contents is at 4%-20%, and alkannic acid content is at 1%-10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%-10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%-6%, and ginsenoside Rg1's content is 15%-40%, and ginsenoside Rb1's content is 15%-40%, ginsenoside Rd's content is 5%-12%, and the content of its Radix Notoginseng total arasaponins is more than 70%; Astragaloside content is 5%-15% in the Radix Astragali extract, and the content of its Radix Astragali total saponins is more than 70%.
4. the Chinese medicinal granule that contains Radix Astragali extract according to claim 1 is characterized in that described pharmaceutically acceptable carrier comprises that in sucrose, dextrin, starch, lactose, mannitol, xylitol, chitosan, SHUANGQITANG, soluble starch, Pulvis Talci, water solublity dextrin sodium carboxymethyl cellulose (CMS-Na), microcrystalline Cellulose (MCC), micropowder silica gel, hydroxypropyl starch, ethanol, hydroxypropyl cellulose, Polyethylene Glycol, chitosan, the polyvidone one or more unite use.
5. as containing the Chinese medicinal granule of Radix Astragali extract as described in the claim 4, it is characterized in that described pharmaceutically acceptable carrier is preferably: microcrystalline Cellulose (MCC), micropowder silica gel, Polyethylene Glycol, Pulvis Talci, chitosan, Pulvis Talci, polyvidone.
6. the Chinese medicinal granule that contains Radix Astragali extract according to claim 1, it is characterized in that described granule comprises master batch and the shell that is positioned on the master batch, profile is sphere or class sphere, bulk density is 0.6～1.3g/m, dissolve scattered time limit is 0.4～5 minute, and active constituents of medicine is included among master batch and/or the shell.
7. the Chinese medicinal granule that contains Radix Astragali extract according to claim 1 is characterized in that its particle diameter is 700～1500 μ m.
8. the Chinese medicinal granule that contains Radix Astragali extract according to claim 1 is characterized in that described granule also contains coating, and the weight of coating materials accounts for 2～5wt% of granule gross weight.
9, each described preparation method that contains the Chinese medicinal granule of Radix Astragali extract of claim 1～7 is characterized in that step is as follows:
(1) preparation of active component of the present invention: Radix Salviae Miltiorrhizae extract 5.0%～70.0%, Radix Notoginseng extract 10.0%～85.0%, Radix Astragali extract 5.0%～70.0% and Borneolum Syntheticum 1.0%～15.0%, mix homogeneously, preparation cost invention active component;
(2) preparation of master batch: i. gets an amount of pharmaceutically acceptable carrier, the perhaps mixture of itself and Chinese medicine extract dry powder, and crushing screening obtains the satisfactory material of granularity; Ii. get the material of a part of step I, drop in spray of fluid bed side or the end spray pot, other gets it filled and learns acceptable carrier and/or Chinese medicine extract and add water and be mixed with slurry, adopt spray of fluid bed side or end pressure spray process to spray into, and sift out granule, again parent nucleus is dropped in the pot as parent nucleus, continue to spray and state slurry, the material of remaining step I is sprinkled into fine powder in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, filter out the satisfactory master batch of particle diameter;
(3) preparation of product: it is an amount of to get master batch, and acceptable carrier is an amount of, and active component of the present invention is an amount of; Above-mentioned acceptable carrier is added in the invention described above active component, and it is standby as slurry to mix into suspension; Above-mentioned master batch is dropped in the fluid bed side spray pot, and above-mentioned slurry slowly sprays into, and all sprays into to slurry, makes spheroidal particle.
10, as containing the preparation method of the Chinese medicinal granule of Radix Astragali extract as described in as described in the claim 9, it is characterized in that step is as follows:
(1) preparation of active component of the present invention: get Radix Salviae Miltiorrhizae extract 23%, Radix Notoginseng extract 45%, Radix Astragali extract 23% and Borneolum Syntheticum 9%, mix homogeneously, preparation cost invention active component;
(2) preparation of master batch: the mixture of getting dextrin and starch weight ratio and be 1:1 is crossed 200 mesh sieves, and wherein 60-65wt% drops in the fluid bed side spray pot as bed material; 10-15wt% dextrin and starch mixture, amount to the active component of the present invention that accounts for the 15wt% of master batch weight after the dry weight, adding water is mixed with slurry and sprays into, and to sift out particle diameter be that 180～250 μ m granules are as parent nucleus, again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle dextrin of surplus and the fine powder of starch mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, the master batch that filters out particle diameter and be 450～600 μ m is standby;
(3) preparation of product: get master batch 450g, the active component of the present invention of 230g, with active component weight ratio of the present invention be 18: 25 polyethylene glycol 6000, perhaps with active component weight ratio of the present invention be 7:25 HPMC and PVP-K30 mixture, wherein the HPMC:PVP-K30 weight ratio is 2:5; With dehydrated alcohol above-mentioned viscosity is adjusted and a kind ofly in agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture to be formulated as the solution that concentration is 15wt%, add in the active component of the present invention, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and make spheroidal particle.
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| CN2007101503169A CN101439078B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing astragalus extract and preparation method thereof |
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| CN2007101503169A CN101439078B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing astragalus extract and preparation method thereof |
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| CN101439078B CN101439078B (en) | 2012-03-28 |
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| CN111686148A (en) * | 2019-11-06 | 2020-09-22 | 成都青之欣生物科技有限公司 | Anti-aging traditional Chinese medicine extract and extraction method and application thereof |
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| CN1486730A (en) * | 2003-07-24 | 2004-04-07 | 上海绿谷（集团）有限公司 | Capsule prepn for regulating blood fat and blood pressure |
| CN100339085C (en) * | 2003-09-23 | 2007-09-26 | 天津天士力制药股份有限公司 | Combination of Chinese traditional medicine for curing cardiovascular and cerebrovascular diseases |
| CN100342859C (en) * | 2004-08-20 | 2007-10-17 | 中国人民解放军军事医学科学院毒物药物研究所 | Method for preparing formulation containing Indianmulberry extract |
| CN1762401A (en) * | 2004-09-24 | 2006-04-26 | 贵阳云岩西创药物科技开发有限公司 | Compound formulation of notoginseng for treating cardiovascular and cerebrovascular diseases, preparation method and application thereof |
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