Summary of the invention
The object of the present invention is to provide a kind of Chinese medicinal granule that contains Radix Salviae Miltiorrhizae extract.
Another object of the present invention is to provide a kind of method for preparing that contains the Chinese medicinal granule of Radix Salviae Miltiorrhizae extract.
The present invention contains the Chinese medicinal granule of Radix Salviae Miltiorrhizae extract and realizes through following technical scheme:
Processed 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 obtained according to following method by following materials of weight proportions: 30~180 parts of Radix Salviae Miltiorrhizaes, 5~40 parts of Radix Notoginseng and 0.3~2.5 part of Borneolum Syntheticum are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 1~5 time, collecting decoction filters; Filtrating concentrates, and adds 0.5~5 times of amount 80~99% ethanol, leaves standstill 12~36 hours; Filter, reclaim ethanol, filtrating is concentrated under 30~80 ℃ of conditions, relative density is 1.05~1.45 thick paste 1; Finely divided ice tablet of Borneolum Syntheticum that perhaps is dissolved in the adequate amount of ethanol joined in the thick paste 1 preparation cost invention Chinese medicine extract.
The present invention contains the Chinese medicinal granule of Radix Salviae Miltiorrhizae extract, preferably realizes through following technical scheme:
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 obtained according to following method by following materials of weight proportions: 75~115 parts of Radix Salviae Miltiorrhizaes, 14~20 parts of Radix Notoginseng and 0.8~1.2 part of Borneolum Syntheticum are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 2~4 times, collecting decoction filters, filtrating concentrates, and adds 1~3 times of amount 90~97% ethanol, leaves standstill 18~30 hours, filters, and reclaims ethanol, filtrate be concentrated under 50~75 ℃ of conditions, relative density is 1.20~1.40 thick paste 1; Finely divided ice tablet of Borneolum Syntheticum that perhaps is dissolved in the adequate amount of ethanol joined in the thick paste 1 preparation cost invention Chinese medicine extract.
The present invention contains the Chinese medicinal granule of Radix Salviae Miltiorrhizae extract, and the best realizes through following technical scheme:
Weight percentage by Chinese medicine extract is 70~80%, and pharmaceutically acceptable vehicle weight percentage composition is 20~30%; Wherein Chinese medicine extract is obtained according to following method by following materials of weight proportions: 90 parts of Radix Salviae Miltiorrhizaes, 17.6 parts of Radix Notoginseng and 1 part of Borneolum Syntheticum are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water three times, collecting decoction filters, filtrating concentrates, and adds 2 times of amount 95% ethanol, leaves standstill 24 hours, filters, and reclaims ethanol, filtrate be concentrated under 55~60 ℃ of conditions, relative density is 1.33~1.35 thick paste 1; The Borneolum Syntheticum that will be dissolved in the adequate amount of ethanol joins in the thick paste 1, preparation cost invention Chinese medicine extract.
Chinese medicine extract described in the present invention; Can obtain according to method provided by the invention; Also can get like the preparation of methods such as decocting method, infusion process, percolation, circumfluence method, water extract-alcohol precipitation, alcohol extracting-water precipitating according to the conventional or commonly used method in present technique field; Can be extractum, also can be the effective site of further extraction separation acquisition or the compositions of effective site.
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 by the function address, are viscosity modifier in this patent; 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 the object of the invention.
The present invention contains the Chinese medicinal granule of Radix Salviae Miltiorrhizae 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 Salviae Miltiorrhizae 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 Salviae Miltiorrhizae extract; Described granule comprises master batch and is positioned at the shell on the master batch, and profile be spherical or type 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 Salviae Miltiorrhizae extract, and its particle diameter is 700~1500 μ m.
The present invention contains the Chinese medicinal granule of Radix Salviae Miltiorrhizae extract, and said 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 Salviae Miltiorrhizae 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 pharmaceutically acceptable carrier and corresponding Chinese medicine extract dry powder.
The present invention contains the method for preparing of the Chinese medicinal granule of Radix Salviae Miltiorrhizae extract, and step is following:
(1) preparation of extract: Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 1~5 time, collecting decoction filters; Filtrating concentrates, and adds 0.5~5 times of amount 80~99% ethanol, leaves standstill 12~36 hours; Filter, reclaim ethanol, filtrating is concentrated under 30~80 ℃ of conditions, relative density is 1.05~1.45 thick paste 1; Finely divided ice tablet of Borneolum Syntheticum that perhaps is dissolved in the adequate amount of ethanol joined in the thick paste 1 preparation cost invention Chinese medicine extract;
(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 extract extractum of the present invention is an amount of; Above-mentioned acceptable carrier is added in the invention described above extract extractum, and it is subsequent use 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, processes spheroidal particle.
The present invention contains the method for preparing of the Chinese medicinal granule of Radix Salviae Miltiorrhizae extract, and preferred steps is following:
(1) preparation of extract: get Radix Salviae Miltiorrhizae 9kg, Radix Notoginseng 1.76kg decocte with water 3 times, decoction liquor is filtered, filtrating concentrates, and precipitate with ethanol left standstill 24 hours, filters, reclaims ethanol, and relative density is 1.33~1.35 when being condensed into thick paste shape to 50~60 ℃, obtains extractum; After getting Borneolum Syntheticum and cyclodextrin or PVP enclose,, obtain compound Salviae Miltiorrhizae extractum with enclose liquid and above-mentioned extractum mix homogeneously, subsequent use;
(2) preparation of master batch: the mixture of getting dextrin and starch weight ratio and being 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 extract extractum of the present invention that accounts for the 15wt% of master batch weight after the dry weight; Add water and be mixed with slurry and spray into, and sift out particle diameter be 180~250 μ m granules as parent nucleus, again parent nucleus is dropped in the pot; Continue to spray and state slurry; In the dusting rifle, the 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 subsequent use;
(3) preparation of product: get the about 450g of master batch; 100~1000g compound Salviae Miltiorrhizae extractum and Borneolum Syntheticum; With compound Salviae Miltiorrhizae extractum weight ratio be 18: 25 polyethylene glycol 6000; Perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with compound Salviae Miltiorrhizae extractum weight ratio: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol with a kind of solution that is formulated as concentration as 15wt% in above-mentioned viscosity adjustment agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture; Add in the compound Salviae Miltiorrhizae extractum; 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 process spheroidal particle.
The present invention contains in the method for preparing of Chinese medicinal granule of Radix Salviae Miltiorrhizae extract, and the temperature of charge of the spheroidal particle that can said method 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, process spheroidal particle, its bulk density is 0.76g/ml, and dissolve scattered time limit is 25 seconds.
The present invention contains in the method for preparing of Chinese medicinal granule of Radix Salviae Miltiorrhizae extract, No. 2 capsules of spheroidal particle fill that can said method be obtained, and the 250mg/ grain is processed 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 Salviae Miltiorrhizae 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 conventional method in this area.
The present invention contains the Chinese medicinal granule of Radix Salviae Miltiorrhizae 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 Salviae Miltiorrhizae extract, and preferred said granule is processed 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, granule of the present invention spherical in shape or type spherical, smooth surface rounding, the control of suitable product design quality.
3. physical characteristic is good, prepares in the process at spheroidal particle, and 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% through a sieve through the granule and the powder summation of No. four sieves.Granule of the present invention can not and can meet the pharmacopeia regulation through the granule and the powder summation of No. four sieves through 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
Below in conjunction with specific embodiment the present invention is further described, following this embodiment only is used to the present invention is described and the present invention is not limited.
Embodiment 1
The extraction of extractum: get Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 3 times, decoction liquor filters, and filtrating concentrates, and precipitate with ethanol left standstill 24 hours, filters, reclaims ethanol, and it is subsequent use to relative density 1.33-1.35 (50-60 ℃) to be condensed into the thick paste shape.After getting Borneolum Syntheticum and cyclodextrin or PVP enclose, enclose liquid and extractum mix homogeneously, subsequent use;
The preparation of master batch: the weight ratio of getting dextrin and starch is that 1: 1 mixture is crossed 200 mesh sieves; 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 sifts out granule (particle diameter is 180-250 μ) as parent nucleus, parent nucleus is dropped in the pot again; 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, it is subsequent use at the master batch of 450 μ-600 μ to filter out particle diameter.
The preparation of product: get the about 450g of master batch, the about 50g of microcrystalline Cellulose (200 order), polyethylene glycol 6000 (heating and melting) are approximately
500G, the extractum of 10000 dosage of extractum; Microcrystalline Cellulose and micropowder silica gel are added in the extractum, 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 be dried to simultaneously slurry and all spray into and process spheroidal particle, temperature of charge is controlled at 55 degrees centigrade, and 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, processes spheroidal particle.Bulk density is 0.76g/ml.With No. 2 capsules of the spheroidal particle fill that obtains, every dress 0.125g processes 10000 of capsules.
Embodiment 2
The extraction of extractum: Radix Salviae Miltiorrhizae 1800g, Radix Notoginseng 400g and Borneolum Syntheticum 3g are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 5 times, collecting decoction filters, filtrating concentrates, and adds 5 times of amount 80% ethanol, leaves standstill 12 hours, filters, and reclaims ethanol, filtrate be concentrated under 80 ℃ of conditions, relative density is 1.05~1.15 thick paste 1; Join in the thick paste 1 preparation cost invention Chinese medicine extract with finely divided ice.
The preparation of master batch: the mixture of getting micropowder silica gel and chitosan weight ratio and being 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 sift out particle diameter be 120-180 μ granule 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, it is subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get the about 300g of master batch, the about 250g of microcrystalline Cellulose (200 order), the about 14g of micropowder silica gel, extractum 200g; Microcrystalline Cellulose and micropowder silica gel are added in the extractum, and it is subsequent use 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 process 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, processes spheroidal particle.Particulate bulk density 0.93g/ml, with No. 00 capsule of the spheroidal particle fill that obtains, every dress 0.70g processes capsule.
Embodiment 3
The extraction of extractum: Radix Salviae Miltiorrhizae 1500g, Radix Notoginseng 70g and Borneolum Syntheticum 25g are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 2 times, collecting decoction filters, filtrating concentrates, and adds 2 times of amount 90% ethanol, leaves standstill 36 hours, filters, and reclaims ethanol, filtrate be concentrated under 30 ℃ of conditions, relative density is 1.05~1.35 thick paste 1; The Borneolum Syntheticum that will be dissolved in the adequate amount of ethanol joins in the thick paste 1, preparation cost invention Chinese medicine extract.
The preparation of master batch: the mixture of getting dextrin and starch weight ratio and being 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 sifts out granule (particle diameter is 180~250 μ) as parent nucleus, parent nucleus is dropped in the pot again; 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, it is subsequent use at the master batch of 300 μ~400 μ to filter out particle diameter.
The preparation of product: get the about 450g of master batch, the about 50g of microcrystalline Cellulose (200 order), polyethylene glycol 6000 (heating and melting) are approximately
500G, extractum 1000g; Microcrystalline Cellulose and micropowder silica gel are added in the extractum, 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 be dried to simultaneously slurry and all spray into and process spheroidal particle, temperature of charge is controlled at 55 degrees centigrade; 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, processes spheroidal particle, and bulk density is 0.76g/ml; With No. 2 capsules of the spheroidal particle fill that obtains, every dress 0.125g processes capsule.
Embodiment 4
The extraction of extractum: it is subsequent use to get Radix Salviae Miltiorrhizae 1150g, Radix Notoginseng 200g and Borneolum Syntheticum 12g; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 4 times, collecting decoction filters, filtrating concentrates, and adds 3 times of amount 90% ethanol, leaves standstill 30 hours, filters, and reclaims ethanol, filtrate be concentrated under 75 ℃ of conditions, relative density is 1.20~1.40 thick paste 1; The Borneolum Syntheticum that will be dissolved in the adequate amount of ethanol joins in the thick paste 1, preparation cost invention Chinese medicine extract.
The preparation of master batch: the mixture of getting dextrin and microcrystalline Cellulose weight ratio and being 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 sift out particle diameter be 180~250 μ granules 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, it is subsequent use at the master batch of 300 μ~400 μ to filter out particle diameter.
The preparation of product: get the about 1000g of master batch, in 5% the polyvidone solution, add extractum an amount of (being equivalent to 50 kilograms of medical materials); In 5% the polyvidone solution, add that extractum is an amount of, adding water, to mix into solid content be that 30% suspension is subsequent use 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 process 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, processes spheroidal particle.
Embodiment 5
The extraction of extractum: it is subsequent use to get Radix Salviae Miltiorrhizae 750g, Radix Notoginseng 140g and Borneolum Syntheticum 8g; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 2 times, collecting decoction filters, filtrating concentrates, and adds 2 times of amount 97% ethanol, leaves standstill 18 hours, filters, and reclaims ethanol, filtrate be concentrated under 50 ℃ of conditions, relative density is 1.20~1.30 thick paste 1; Join in the thick paste 1 preparation cost invention Chinese medicine extract with finely divided ice.
The preparation of master batch: the mixture of getting dextrin and microcrystalline Cellulose weight ratio and being 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 sift out particle diameter be 100-200 μ granule 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, it is subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get the about 800g of master batch, the about 190g of microcrystalline Cellulose, the about 35g of micropowder silica gel, extractum 250g; Microcrystalline Cellulose and micropowder silica gel are added in the extractum, and it is subsequent use 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 process spheroidal particle.
Embodiment 6
The extraction of extractum: it is subsequent use to get Radix Salviae Miltiorrhizae 900g, Radix Notoginseng 176g and Borneolum Syntheticum 10g; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water three times, collecting decoction filters, filtrating concentrates, and adds 2 times of amount 95% ethanol, leaves standstill 24 hours, filters, and reclaims ethanol, filtrate be concentrated under 55~60 ℃ of conditions, relative density is 1.33~1.35 thick paste 1; The Borneolum Syntheticum that will be dissolved in the adequate amount of ethanol joins in the thick paste 1, preparation cost invention Chinese medicine extract.
The preparation of master batch: the mixture of getting micropowder silica gel and Pulvis Talci weight ratio and being 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 and sprays into as slurry, and sift out particle diameter be 120-180 μ granule 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, it is subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get the about 300g of master batch, the about 250g of microcrystalline Cellulose (200 order), the about 14g of micropowder silica gel, extractum 320g; Microcrystalline Cellulose and micropowder silica gel are added in the extractum, and it is subsequent use 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 process spheroidal particle.
Embodiment 7
The extraction of extractum: it is subsequent use to get Radix Salviae Miltiorrhizae 900g, Radix Notoginseng 176g and Borneolum Syntheticum 10g; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water three times, collecting decoction filters, filtrating concentrates, and adds 2 times of amount 95% ethanol, leaves standstill 24 hours, filters, and reclaims ethanol, filtrate be concentrated under 55 ℃ of conditions, relative density is 1.33~1.35 thick paste 1; The Borneolum Syntheticum that will be dissolved in the adequate amount of ethanol joins in the thick paste 1, preparation cost invention Chinese medicine extract.
The preparation of master batch: taking polyethylene glycol and chitosan weight ratio are that 1: 1 mixture 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 sift out particle diameter be 120-180 μ granule 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, it is subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get the about 700g of master batch, the about 300g of microcrystalline Cellulose (200 order), the about 20g of micropowder silica gel, extractum 650g; Microcrystalline Cellulose and micropowder silica gel are added in the extractum, and it is subsequent use 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 process spheroidal particle.
Embodiment 8:
1, the extraction of compound Salviae Miltiorrhizae extractum
Get Radix Salviae Miltiorrhizae 9kg, Radix Notoginseng 1.76kg decocte with water 3 times, decoction liquor is filtered, filtrating concentrates, and precipitate with ethanol left standstill 24 hours, filters, reclaims ethanol, and being condensed into thick paste shape to relative density is 1.33~1.35 (50~60 ℃), obtains extractum.After getting Borneolum Syntheticum and cyclodextrin or PVP enclose,, obtain compound Salviae Miltiorrhizae extractum with enclose liquid and above-mentioned extractum mix homogeneously, subsequent use.
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, and 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), again parent nucleus is dropped in the pot as parent nucleus; 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, it is subsequent use at the master batch of 450~600 μ m to filter out particle diameter.
3, the selection of viscosity adjustment agent
A. get above-mentioned compound Salviae Miltiorrhizae extractum, 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, is prone to scrape 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, be prone to characteristics such as powder; Select viscosity adjustment agent; Experiment shows can select HPMC: PVP-K30 (2: 5) mixture to adjust agent as viscosity, and also can select polyethylene glycol 6000 is viscosity adjustment agent.
D. selection and compound Salviae Miltiorrhizae extractum weight ratio are 7: 25 HPMC: PVP-K30 (2: 5) mixture is viscosity adjustment agent; Perhaps selection and compound Salviae Miltiorrhizae extractum weight ratio are that 18: 25 polyethylene glycol 6000 is viscosity adjustment agent, are increased to 16MPaS to material viscosity by 9.0MPaS.
4, the preparation of compound Salviae Miltiorrhizae spheroidal particle
A. get the about 450g of master batch, with compound Salviae Miltiorrhizae extractum weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC: PVP-K30 (2: 5) mixture, 450g compound Salviae Miltiorrhizae extractum and Borneolum Syntheticum with compound Salviae Miltiorrhizae extractum weight ratio;
B. use dehydrated alcohol with a kind of solution that is formulated as concentration as 15wt% in the above-mentioned viscosity adjustment agent, add in the compound Salviae Miltiorrhizae extractum, 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 be dried to slurry simultaneously and all spray into and process 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, process 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 the spheroidal particle fill that obtains among the step c, the 250mg/ grain is processed capsule.
Embodiment 9
1, the extraction of extractum: Radix Salviae Miltiorrhizae 30kg, Radix Notoginseng 5kg and Borneolum Syntheticum 0.3kg are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 5 times, collecting decoction filters, filtrating concentrates, and adds 5 times of amount 80% ethanol, leaves standstill 12 hours, filters, and reclaims ethanol, filtrate be concentrated under 30 ℃ of conditions, relative density is 1.05~1.45 thick paste 1; Finely divided ice tablet of Borneolum Syntheticum that perhaps is dissolved in the adequate amount of ethanol joined in the thick paste 1 preparation cost invention Chinese medicine extract.
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, and other gets 10wt% xylitol and carboxymethyl starch sodium (1: 1) mixture and extract extractum of the present invention (after amounting to dry weight, accounting for the 15wt% of master batch weight) and adds 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 subsequent use.
3, the preparation of product: get the about 450g of master batch; 350g compound Salviae Miltiorrhizae extractum and Borneolum Syntheticum, with compound Salviae Miltiorrhizae extractum weight ratio be 18: 25 polyethylene glycol 6000, use dehydrated alcohol that above-mentioned viscosity adjustment agent polyethylene glycol 6000 is formulated as the solution of concentration as 15wt%; Add in the compound Salviae Miltiorrhizae extractum; 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 process spheroidal particle.
Embodiment 10
1, the extraction of extractum: Radix Salviae Miltiorrhizae 180kg, Radix Notoginseng 40kg and Borneolum Syntheticum 2.5kg are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 3 times, collecting decoction filters, filtrating concentrates, and adds 3 times of amount 96% ethanol, leaves standstill 36 hours, filters, and reclaims ethanol, filtrate be concentrated under 80 ℃ of conditions, relative density is 1.05~1.45 thick paste 1; Finely divided ice tablet of Borneolum Syntheticum that perhaps is dissolved in the adequate amount of ethanol joined in the thick paste 1 preparation cost invention Chinese medicine extract.
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, and other gets 10wt% lactose and hydroxypropyl starch (1: 1) mixture and extract extractum of the present invention (after amounting to dry weight, accounting for the 15wt% of master batch weight) and adds 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 subsequent use.
3, the preparation of product: get the about 850g of master batch, 1000g compound Salviae Miltiorrhizae extractum and Borneolum Syntheticum, with compound Salviae Miltiorrhizae extractum weight ratio be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol that above-mentioned viscosity adjustment agent HPMC is formulated as the solution of concentration as 15wt% with the PVP-K30 mixture, in the adding compound Salviae Miltiorrhizae extractum, 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 process spheroidal particle.
Embodiment 11
1, the extraction of extractum: Radix Salviae Miltiorrhizae 115kg, Radix Notoginseng 20kg and Borneolum Syntheticum 1.2kg are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 2 times, collecting decoction filters, filtrating concentrates, and adds 3 times of amount 97% ethanol, leaves standstill 30 hours, filters, and reclaims ethanol, filtrate be concentrated under 75 ℃ of conditions, relative density is 1.20~1.40 thick paste 1; Finely divided ice tablet of Borneolum Syntheticum that perhaps is dissolved in the adequate amount of ethanol joined in the thick paste 1 preparation cost invention Chinese medicine extract.
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, and other gets 16wt% dextrin and mannitol mixture and extract extractum of the present invention (after amounting to dry weight, accounting for the 10wt% of master batch weight) and adds 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 subsequent use.
3, the preparation of product: get the about 500g of master batch, 550g compound Salviae Miltiorrhizae extractum and Borneolum Syntheticum, with compound Salviae Miltiorrhizae extractum weight ratio be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol that above-mentioned viscosity adjustment agent HPMC is formulated as the solution of concentration as 15wt% with the PVP-K30 mixture, in the adding compound Salviae Miltiorrhizae extractum, 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 process spheroidal particle.
Embodiment 12
1, the extraction of extractum: Radix Salviae Miltiorrhizae 75kg, Radix Notoginseng 14kg and Borneolum Syntheticum 0.8kg are subsequent use; Radix Salviae Miltiorrhizae, Radix Notoginseng decocte with water 4 times, collecting decoction filters, filtrating concentrates, and adds 2 times of amount 90% ethanol, leaves standstill 18 hours, filters, and reclaims ethanol, filtrate be concentrated under 50 ℃ of conditions, relative density is 1.20~1.40 thick paste 1; Finely divided ice tablet of Borneolum Syntheticum that perhaps is dissolved in the adequate amount of ethanol joined in the thick paste 1 preparation cost invention Chinese medicine extract.
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, and other gets 25wt% dextrin and mannitol mixture and extract extractum of the present invention (after amounting to dry weight, accounting for the 10wt% of master batch weight) and adds 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 subsequent use.
3, the preparation of product: get the about 450g of master batch; 850g compound Salviae Miltiorrhizae extractum and Borneolum Syntheticum, with compound Salviae Miltiorrhizae extractum weight ratio be 18: 25 polyethylene glycol 6000, use dehydrated alcohol that above-mentioned viscosity adjustment agent polyethylene glycol 6000 is formulated as the solution of concentration as 15wt%; Add in the compound Salviae Miltiorrhizae extractum; 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 process spheroidal particle.