CN101439062A - Chinese medicine granule containing andrographolide and preparation method thereof - Google Patents
Chinese medicine granule containing andrographolide and preparation method thereof Download PDFInfo
- Publication number
- CN101439062A CN101439062A CNA200710150321XA CN200710150321A CN101439062A CN 101439062 A CN101439062 A CN 101439062A CN A200710150321X A CNA200710150321X A CN A200710150321XA CN 200710150321 A CN200710150321 A CN 200710150321A CN 101439062 A CN101439062 A CN 101439062A
- Authority
- CN
- China
- Prior art keywords
- andrographolide
- master batch
- slurry
- spray
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 62
- 239000003814 drug Substances 0.000 title claims abstract description 28
- BOJKULTULYSRAS-OTESTREVSA-N Andrographolide Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/[C@H](O)COC1=O BOJKULTULYSRAS-OTESTREVSA-N 0.000 title claims description 122
- ASLUCFFROXVMFL-UHFFFAOYSA-N andrographolide Natural products CC1(CO)C(O)CCC2(C)C(CC=C3/C(O)OCC3=O)C(=C)CCC12 ASLUCFFROXVMFL-UHFFFAOYSA-N 0.000 title claims description 122
- 239000008187 granular material Substances 0.000 title claims description 77
- 239000002245 particle Substances 0.000 claims abstract description 100
- 239000003937 drug carrier Substances 0.000 claims abstract description 14
- 239000007921 spray Substances 0.000 claims description 100
- 239000002002 slurry Substances 0.000 claims description 85
- 239000004594 Masterbatch (MB) Substances 0.000 claims description 82
- 239000000203 mixture Substances 0.000 claims description 55
- 238000000576 coating method Methods 0.000 claims description 41
- 239000011248 coating agent Substances 0.000 claims description 40
- 229920002472 Starch Polymers 0.000 claims description 39
- 239000008107 starch Substances 0.000 claims description 39
- 235000019698 starch Nutrition 0.000 claims description 39
- 239000012530 fluid Substances 0.000 claims description 38
- 239000000463 material Substances 0.000 claims description 34
- 229920001353 Dextrin Polymers 0.000 claims description 32
- 239000004375 Dextrin Substances 0.000 claims description 32
- 235000019425 dextrin Nutrition 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 239000000843 powder Substances 0.000 claims description 28
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 26
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 26
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 26
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 26
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 23
- 229920003081 Povidone K 30 Polymers 0.000 claims description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- 239000000741 silica gel Substances 0.000 claims description 20
- 229910002027 silica gel Inorganic materials 0.000 claims description 20
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 18
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 18
- 238000010410 dusting Methods 0.000 claims description 17
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 13
- 229920001661 Chitosan Polymers 0.000 claims description 12
- 229960004756 ethanol Drugs 0.000 claims description 11
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 10
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 9
- 229930195725 Mannitol Natural products 0.000 claims description 9
- 239000000594 mannitol Substances 0.000 claims description 9
- 235000010355 mannitol Nutrition 0.000 claims description 9
- 229920001223 polyethylene glycol Polymers 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 238000012546 transfer Methods 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 6
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 6
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 6
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 6
- 239000008101 lactose Substances 0.000 claims description 6
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 239000003981 vehicle Substances 0.000 claims description 6
- 239000000811 xylitol Substances 0.000 claims description 6
- 235000010447 xylitol Nutrition 0.000 claims description 6
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 6
- 229960002675 xylitol Drugs 0.000 claims description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 239000000470 constituent Substances 0.000 claims description 2
- 235000019441 ethanol Nutrition 0.000 claims description 2
- 238000012216 screening Methods 0.000 claims description 2
- 239000002775 capsule Substances 0.000 abstract description 11
- 239000003405 delayed action preparation Substances 0.000 abstract description 5
- 239000011265 semifinished product Substances 0.000 abstract 1
- 230000002459 sustained effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 17
- 238000005516 engineering process Methods 0.000 description 14
- 239000000284 extract Substances 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 206010057190 Respiratory tract infections Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 241000746375 Andrographis Species 0.000 description 2
- 208000004429 Bacillary Dysentery Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 206010017915 Gastroenteritis shigella Diseases 0.000 description 2
- 206010022678 Intestinal infections Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 2
- 239000007767 bonding agent Substances 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 210000000589 cicatrix Anatomy 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 201000005113 shigellosis Diseases 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 206010034038 Parotitis Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010035737 Pneumonia viral Diseases 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 206010047482 Viral upper respiratory tract infection Diseases 0.000 description 1
- 208000012876 acute enteritis Diseases 0.000 description 1
- 206010001093 acute tonsillitis Diseases 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 208000021735 chronic enteritis Diseases 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000011868 grain product Nutrition 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 238000005325 percolation Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 238000005563 spheronization Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000009421 viral pneumonia Diseases 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a traditional Chinese medicine granular preparation with andrographolidume and a preparation method thereof. Traditional Chinese medicine spheroidized particles are prepared by using andrographolidume 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 andrographolide and preparation method thereof.
Background technology
Andrographolide (Andrographolide) claims andrographolide again, for the crystallization of colourless square, rectangle or prism-shaped, is the diterpenic lactone that extracts from the Herba Andrographis medical material.Record in one one of Pharmacopoeia of People's Republic of China [version in 1997].Be widely used for the treatment of multiple infection and non-infectious inflammatory diseases clinically, especially the curative effect with intestinal and respiratory tract infection is good.
The intestinal infection aspect, andrographolide all has certain curative effect to acute chronic enteritis, bacillary dysentery, ileotyphus and intestinal infusorian, but being good to acute bacillary dysentery and acute enteritis curative effect.Respiratory tract infection aspect, the Chinese medicine patent medicine of multiple treatment upper respiratory tract infection are principal agent with Herba Andrographis all, and clinical practice is very wide.Wherein especially preferable to viral pneumonia and upper respiratory tract infection curative effect.In addition, flu, influenza, parotitis, pharyngitis, popular asthma pneumonia, acute tonsillitis and cough etc. also there is certain curative effect.
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 andrographolide, 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 andrographolide.
Another object of the present invention is to provide a kind of preparation method that contains the Chinese medicinal granule of andrographolide.
The Chinese medicinal granule that the present invention contains andrographolide is achieved through the following technical solutions:
Made by andrographolide and pharmaceutically acceptable carrier, wherein andrographolide accounts for 40～90% of percentage by weight, and pharmaceutically acceptable vehicle weight percentage composition is 10～60%.
The present invention contains the Chinese medicinal granule of andrographolide, preferably is achieved through the following technical solutions:
Weight percentage by andrographolide is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%.
The present invention contains the Chinese medicinal granule of andrographolide, and the best is achieved through the following technical solutions:
Weight percentage by andrographolide is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%.
Andrographolide 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.
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 andrographolide, 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 andrographolide, 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 andrographolide, 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 andrographolide, and its particle diameter is 700～1500 μ m.
The present invention contains the Chinese medicinal granule of andrographolide, 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 andrographolide 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 andrographolide dry powder.
The present invention contains the preparation method of the Chinese medicinal granule of andrographolide, and step is as follows:
(1) it is an amount of to get andrographolide;
(2) preparation of master batch: i. gets an amount of pharmaceutically acceptable carrier, the perhaps mixture of itself and andrographolide 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 andrographolide 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 andrographolide is an amount of; Above-mentioned acceptable carrier is added in the above-mentioned andrographolide, 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 andrographolide, and preferred steps is as follows:
It is an amount of to get andrographolide;
(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 andrographolide 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 andrographolide of 300g, with the andrographolide weight ratio be the polyethylene glycol 6000 of 18:25, be HPMC and the PVP-K30 mixture of 7:25 perhaps with the andrographolide weight ratio, 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 andrographolide, 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 andrographolide, 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 andrographolide, No. 2 capsules of spheroidal particle fill that said method can be obtained, and the 250mg/ grain is made capsule.
" 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 andrographolide, 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 andrographolide, 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 andrographolide, 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
It is an amount of to get andrographolide;
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, andrographolide 320g; Microcrystalline Cellulose and micropowder silica gel are added in the andrographolide, 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, 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 2
It is an amount of to get andrographolide;
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, andrographolide 200g; Microcrystalline Cellulose and micropowder silica gel are added in the andrographolide, 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.
Embodiment 3
It is an amount of to get andrographolide;
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, andrographolide 1000g; Microcrystalline Cellulose and micropowder silica gel are added in the andrographolide, 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, 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, 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
It is an amount of to get andrographolide;
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, add andrographolide 750g, 5% polyvidone solution, 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
It is an amount of to get andrographolide;
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 and sprays 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, andrographolide 450g; Microcrystalline Cellulose and micropowder silica gel are added in the andrographolide, 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
It is an amount of to get andrographolide;
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, andrographolide 300g; Microcrystalline Cellulose and micropowder silica gel are added in the andrographolide, 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
It is an amount of to get andrographolide;
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, andrographolide 430g; Microcrystalline Cellulose and micropowder silica gel are added in the andrographolide, 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, it is an amount of to get andrographolide;
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 above-mentioned andrographolide, 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. selection and andrographolide weight ratio are that HPMC:PVP-K30 (2:5) mixture of 7:25 is that viscosity is adjusted agent, perhaps selection and andrographolide weight ratio are that the polyethylene glycol 6000 of 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 andrographolide weight ratio be the polyethylene glycol 6000 of 18:25, perhaps be HPMC:PVP-K30 (2:5) mixture of 7:25 with the andrographolide weight ratio, the andrographolide of 340g;
B. with dehydrated alcohol above-mentioned viscosity is adjusted and a kind ofly in the agent be formulated as the solution that concentration is 5wt%, add in the andrographolide, 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 30 seconds.
With No. 2 capsules of spheroidal particle fill that obtain among the step c, the 250mg/ grain is made capsule.
Embodiment 9
1, it is an amount of to get andrographolide.
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 andrographolide (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 andrographolide of 440g, with the andrographolide weight ratio be the polyethylene glycol 6000 of 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 andrographolide, 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, it is an amount of to get andrographolide;
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 andrographolide (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 andrographolide of 500g, with the andrographolide weight ratio be HPMC and the PVP-K30 mixture of 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 andrographolide, 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, it is an amount of to get andrographolide;
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 andrographolide (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, the andrographolide of 500g, with the andrographolide weight ratio be HPMC and the PVP-K30 mixture of 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 andrographolide, 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, it is an amount of to get andrographolide;
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 andrographolide (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 andrographolide of 800g, with the andrographolide weight ratio be the polyethylene glycol 6000 of 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 andrographolide, 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 13
1, it is an amount of to get andrographolide;
2, the 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 andrographolide 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, the preparation of product: get master batch 450g, the andrographolide of 300g, with the andrographolide weight ratio be the polyethylene glycol 6000 of 18:25, be HPMC and the PVP-K30 mixture of 7:25 perhaps with the andrographolide weight ratio, 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 andrographolide, 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 andrographolide is made by andrographolide and pharmaceutically acceptable carrier, it is characterized in that andrographolide accounts for 40～90% of percentage by weight, and pharmaceutically acceptable vehicle weight percentage composition is 10～60%.
2. the Chinese medicinal granule that contains andrographolide according to claim 1, the weight percentage that it is characterized in that andrographolide is 70～80%, pharmaceutically acceptable vehicle weight percentage composition is 20～30%.
3. as containing the Chinese medicinal granule of andrographolide as described in the claim 2, the weight percentage that it is characterized in that andrographolide is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%.
4. the Chinese medicinal granule that contains andrographolide 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 andrographolide 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 andrographolide 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 andrographolide according to claim 1 is characterized in that its particle diameter is 700～1500 μ m.
8. the Chinese medicinal granule that contains andrographolide 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 andrographolide of claim 1～7 is characterized in that step is as follows:
(1) it is an amount of to get andrographolide;
(2) preparation of master batch: i. gets an amount of pharmaceutically acceptable carrier, the perhaps mixture of itself and andrographolide 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 andrographolide 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 andrographolide is an amount of; Above-mentioned acceptable carrier is added in the above-mentioned andrographolide, 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 andrographolide as described in as described in the claim 9, it is characterized in that step is as follows:
(1) it is an amount of to get andrographolide;
(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 andrographolide 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 andrographolide of 300g, with the andrographolide weight ratio be the polyethylene glycol 6000 of 18:25, be HPMC and the PVP-K30 mixture of 7:25 perhaps with the andrographolide weight ratio, 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 andrographolide, 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710150321XA CN101439062B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing andrographolide and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710150321XA CN101439062B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing andrographolide and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101439062A true CN101439062A (en) | 2009-05-27 |
| CN101439062B CN101439062B (en) | 2012-07-18 |
Family
ID=40723760
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200710150321XA Active CN101439062B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing andrographolide and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101439062B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102240282A (en) * | 2011-05-05 | 2011-11-16 | 中国人民解放军军事医学科学院毒物药物研究所 | Potassium dehydroandrographolide succinate oral pharmaceutical composition and preparation method thereof |
| CN104274440A (en) * | 2013-07-11 | 2015-01-14 | 成都中医药大学 | Andrographolide composite particles and preparation method thereof |
| CN110585138A (en) * | 2019-09-29 | 2019-12-20 | 黑龙江中医药大学 | Andrographis paniculata granules and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN1762347A (en) * | 2004-09-24 | 2006-04-26 | 贵阳云岩西创药物科技开发有限公司 | Andrographolide preparation and its production method |
-
2007
- 2007-11-22 CN CN200710150321XA patent/CN101439062B/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102240282A (en) * | 2011-05-05 | 2011-11-16 | 中国人民解放军军事医学科学院毒物药物研究所 | Potassium dehydroandrographolide succinate oral pharmaceutical composition and preparation method thereof |
| CN104274440A (en) * | 2013-07-11 | 2015-01-14 | 成都中医药大学 | Andrographolide composite particles and preparation method thereof |
| CN104274440B (en) * | 2013-07-11 | 2017-04-26 | 成都中医药大学 | Andrographolide composite particles and preparation method thereof |
| CN110585138A (en) * | 2019-09-29 | 2019-12-20 | 黑龙江中医药大学 | Andrographis paniculata granules and preparation method thereof |
| CN110585138B (en) * | 2019-09-29 | 2021-08-03 | 黑龙江中医药大学 | Andrographis paniculata granules and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101439062B (en) | 2012-07-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101472565B (en) | Preparation method of granular formulation | |
| CN101439076B (en) | Preparation method of chinese medicine granule containing dalbergia heartwood oil | |
| CN101439057B (en) | Chinese medicine granule containing gingko extract and preparation method thereof | |
| CN101439062B (en) | Chinese medicine granule containing andrographolide and preparation method thereof | |
| CN101439135B (en) | Chinese medicine granule containing extract of grassleaved sweetflag rhizome and preparation method thereof | |
| CN101439067B (en) | Chinese medicine granular containing ginseng extract and preparation method thereof | |
| CN101439041B (en) | Chinese medicine granule containing breviscapine and preparation method thereof | |
| CN101439063B (en) | Chinese medicine granular formulation containing Chinese angelica extract and preparation method thereof | |
| CN101439068B (en) | Chinese medicine granule containing silymarin and preparation method thereof | |
| CN101439084B (en) | Chinese medicine granule containing agastache extract and preparation method thereof | |
| CN101439087B (en) | Chinese medicine granule containing salvia root extract and preparation method thereof | |
| CN101439107B (en) | Chinese medicine granule containing haw thorn extract and preparation method thereof | |
| CN101439066B (en) | Chinese medicine granular containing notoginseng extract and preparation method thereof | |
| CN101439065B (en) | Chinese medicine granular containing notoginseng extract and preparation method thereof | |
| CN101439086B (en) | Chinese medicine granule containing total phenolic acids in salvia root and preparation method thereof | |
| CN101439126B (en) | Chinese medicine granule containing Huangyangning and preparation method thereof | |
| CN101439079B (en) | Preparation method of Chinese medicine granule containing total saponins in astragalus | |
| CN101439122B (en) | Chinese medicine granule containing prepared rehmannia root extract and preparation method thereof | |
| CN101439082B (en) | Chinese medicine granule containing sophora root extract and preparation method thereof | |
| CN101439085B (en) | Chinese medicine granule containing agastache extract and preparation method thereof | |
| CN101439058B (en) | Compound Chinese medicine gingko granule and preparation method thereof | |
| CN101439078B (en) | Chinese medicine granule containing astragalus extract and preparation method thereof | |
| CN101439099B (en) | Chinese medicine granule containing red paeonia extract and preparation method thereof | |
| CN101439143B (en) | Chinese medicine granules containing Anemarrhena asphodefoides extract and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: TASLY PHARMACEUTICAL GROUP CO., LTD. Free format text: FORMER NAME: TIANJIN TASLY PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 300410 Tianjin City Hedong District of Beichen Puji Road No. 2 city of the modern Chinese Medicine Patentee after: Tasly Pharmaceutical Group Co., Ltd. Address before: 300410 Tianjin City Hedong District of Beichen Puji Road No. 2 city of the modern Chinese Medicine Patentee before: Tianjin Tianshili Pharmaceutical Co., Ltd. |
|
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 300410 Tianjin city Beichen District Huaihe road and road intersection Dingjiang tianzhijiao Park forensic Center for Intellectual Property Department Patentee after: Tasly Pharmaceutical Group Limited by Share Ltd Address before: 300410 Tianjin City Hedong District of Beichen Puji Road No. 2 city of the modern Chinese Medicine Patentee before: Tasly Pharmaceutical Group Co., Ltd. |