CN101439068B - Chinese medicine granule containing silymarin and preparation method thereof - Google Patents
Chinese medicine granule containing silymarin and preparation method thereof Download PDFInfo
- Publication number
- CN101439068B CN101439068B CN2007101503262A CN200710150326A CN101439068B CN 101439068 B CN101439068 B CN 101439068B CN 2007101503262 A CN2007101503262 A CN 2007101503262A CN 200710150326 A CN200710150326 A CN 200710150326A CN 101439068 B CN101439068 B CN 101439068B
- Authority
- CN
- China
- Prior art keywords
- silymarin
- master batch
- preparation
- slurry
- granule
- 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.)
- Active
Links
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 title claims abstract description 92
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 title claims abstract description 92
- 229960004245 silymarin Drugs 0.000 title claims abstract description 92
- 235000017700 silymarin Nutrition 0.000 title claims abstract description 92
- 238000002360 preparation method Methods 0.000 title claims abstract description 63
- 239000003814 drug Substances 0.000 title claims abstract description 26
- 239000008187 granular material Substances 0.000 title claims description 73
- 239000002245 particle Substances 0.000 claims abstract description 97
- 239000007921 spray Substances 0.000 claims description 91
- 239000002002 slurry Substances 0.000 claims description 80
- 239000004594 Masterbatch (MB) Substances 0.000 claims description 78
- 239000000203 mixture Substances 0.000 claims description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- 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 37
- 239000008107 starch Substances 0.000 claims description 37
- 235000019698 starch Nutrition 0.000 claims description 37
- 239000012530 fluid Substances 0.000 claims description 35
- 239000000463 material Substances 0.000 claims description 31
- 229920001353 Dextrin Polymers 0.000 claims description 30
- 239000004375 Dextrin Substances 0.000 claims description 30
- 235000019425 dextrin Nutrition 0.000 claims description 30
- 239000000843 powder Substances 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 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
- 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 16
- SEBFKMXJBCUCAI-DBMPWETRSA-N silybin Chemical compound C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-DBMPWETRSA-N 0.000 claims description 16
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 15
- 239000004034 viscosity adjusting agent Substances 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 13
- 229960004756 ethanol Drugs 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 10
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 8
- 238000012546 transfer Methods 0.000 claims description 8
- 235000008495 Chrysanthemum leucanthemum Nutrition 0.000 claims description 3
- 235000000604 Chrysanthemum parthenium Nutrition 0.000 claims description 3
- 241000320380 Silybum Species 0.000 claims description 3
- 235000013399 edible fruits Nutrition 0.000 claims description 3
- 235000008384 feverfew Nutrition 0.000 claims description 3
- 238000007670 refining Methods 0.000 claims description 3
- 239000000470 constituent Substances 0.000 claims description 2
- 240000004460 Tanacetum coccineum Species 0.000 claims 1
- 239000002775 capsule Substances 0.000 abstract description 11
- 239000003937 drug carrier 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 22
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 22
- 239000008108 microcrystalline cellulose Substances 0.000 description 22
- 229940016286 microcrystalline cellulose Drugs 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 238000000034 method Methods 0.000 description 16
- 229920001661 Chitosan Polymers 0.000 description 9
- 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 description 8
- 229930195725 Mannitol Natural products 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 239000000594 mannitol Substances 0.000 description 8
- 235000010355 mannitol Nutrition 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 7
- 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 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 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 description 5
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000001341 hydroxy propyl starch Substances 0.000 description 5
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- 239000000811 xylitol Substances 0.000 description 5
- 235000010447 xylitol Nutrition 0.000 description 5
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 5
- 229960002675 xylitol Drugs 0.000 description 5
- 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 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 206010008909 Chronic Hepatitis Diseases 0.000 description 3
- 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
- 239000007767 bonding agent Substances 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
- 238000010438 heat treatment Methods 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 210000004185 liver Anatomy 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
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 244000192528 Chrysanthemum parthenium Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 description 2
- 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 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
- 239000001768 carboxy methyl cellulose 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
- 238000004090 dissolution Methods 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
- 230000006870 function Effects 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 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
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 206010019759 Hepatitis chronic persistent Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- UQOFGTXDASPNLL-XHNCKOQMSA-N Muscarine Chemical compound C[C@@H]1O[C@H](C[N+](C)(C)C)C[C@H]1O UQOFGTXDASPNLL-XHNCKOQMSA-N 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 244000272459 Silybum marianum Species 0.000 description 1
- 235000010841 Silybum marianum Nutrition 0.000 description 1
- 231100000354 acute hepatitis Toxicity 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
- 239000003513 alkali Substances 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- 235000019636 bitter flavor Nutrition 0.000 description 1
- 210000000170 cell membrane Anatomy 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
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019441 ethanol Nutrition 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
- 239000000945 filler Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000011868 grain product Nutrition 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 231100000334 hepatotoxic Toxicity 0.000 description 1
- 230000003082 hepatotoxic effect Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000003908 liver function Effects 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
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012216 screening 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
- 238000005987 sulfurization reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a traditional Chinese medicine granular preparation with silymarin and a preparation method thereof. Traditional Chinese medicine spheroidized particles are prepared by using a silymarin extract and a pharmaceutically acceptable carrier. The shapes of the traditional Chinese medicine spheroidized particles are spherical or similar to spheres, and the density of the traditional Chinese medicine spheroidized particles ranges from 0.6 g/ml to 1.3 g/ml. A single dose of the spheroidized particles is small, the medicine taking is convenient, and the granular preparation can be used as a semifinished product of capsules and can also be used for developing sustained and controlled release preparations of traditional Chinese medicine.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation and preparation method thereof, be specifically related to Chinese medicinal granule of a kind of containing silymarin and preparation method thereof.
Background technology
Silymarin (Silymarn) is through extracting refining gained bulky powder by feverfew Silybum Herba Silybi mariani [Silybum marianum (L) Gaertn] fruit, mildly bitter flavor, have and draw moistly, water insoluble, obvious protection is arranged and stablize the liver plasma membrane effect; The all kinds hepatic injury that the hepatotoxic agents such as carbon tetrachloride, sulfuration acetamide, muscarine, pig urine bean alkali are caused has protection and therapeutical effect in various degree, and the rising of the caused alanine aminotransferase of carbon tetrachloride is had certain interception.The treatment clinical in chronic persistent hepatitis, chronic active hepatitis, that first cirrhosis, liver poisoning etc. are sick is significantly improved for acute hepatitis, chronic hepatitis patient's symptom, sign, liver function.
The Liver-Restoring Tablet that has silymarin tablet, liver aid troche and German MADAUS pharmaceutical factory to produce of selling in the market, because silymarin is water insoluble, hydrophobicity is strong, make dissolution and the dissolution rate of silymarin tablet, Yiganling tablet, Liver-Restoring Tablet low, absorption difference, bioavailability is low, the supplementary product consumption ratio is large, child, old people, bed patient and dysphagia patients are taken inconvenience, and compliance is poor, have affected the performance of silymarin therapeutical effect.
Traditional preparation 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, during for the patient with mixing in water for oral taking or swallow.At present common several Preparation Technology of Granules and the defective of existence thereof: 1. conventional particles preparation technology, because Chinese medical concrete viscosity is higher, the preparation method of conventional particles exists mostly that the drug loading of granule is low, outward appearance is not attractive in appearance, the problems such as mouthfeel is poor, the easy moisture absorption.2. present comparatively popular fluidized bed granulation technology, 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, then begin evenly to spray into binder liq, powder begins coalescent granulating, through spraying and drying repeatedly, when granular size meets the requirements, stop spraying, continue dry.This technique can be reduced to the adjuvant amount more than 50% by traditional 80%, and the single dose of the grain products of preparation generally can be reduced to 3g to 5g by traditional 10g, but used adjuvant can not further reduce, and single dose dosage is larger, and patient compliance is relatively poor; And use this kind method to be not suitable for making the solid preparations such as capsule; Adopting in addition the granule of fluidized bed granulation technology preparation at present commonly used is cellular, irregular shape; Moisture absorption is more common, and inconvenience is preserved; The specific surface area of granule is larger, is not suitable for coating.3. also having Chinese medicine or plant amedica extract is the research of the micropill technique of 700～1500 μ m with fluidized-bed process manufacturing particle diameter, but this technique 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.The micropill dissolve scattered time limit that at present adopts this explained hereafter is generally all at 40 minutes, and the defective such as production process is comparatively complicated, cost is high, the influence factor is more (such as not making when air humidity is large), loss is larger.4. also have to adopt in formulation art and extrude round or extrude the technique that spheronization is made micropill or spheroidal particle, this technique 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 spray technique at the bottom of the fluid bed of employing are also arranged, make Western medicine micropill or spheroidal particle, multiplex in the exploitation of slow releasing preparation, so the product of exploitation generally has slow controlled release characteristics, do not possess the rapid release characteristic.
Quick release and the quick acting of Chinese medicine are importances of the modernization of Chinese medicine, adopt Chinese medicine or the plant amedica granule of manufacturing of the present invention to have the characteristic that leaches fast.
Summary of the invention
The object of the present invention is to provide a kind of Chinese medicinal granule of containing silymarin.
Another object of the present invention is to provide a kind of preparation method of Chinese medicinal granule of containing silymarin.
The Chinese medicinal granule of containing silymarin of the present invention is achieved through the following technical solutions: made by silymarin and pharmaceutically acceptable carrier, wherein silymarin accounts for 40～90% of percentage by weight, and pharmaceutically acceptable vehicle weight percentage composition is 10～60%.
The Chinese medicinal granule of containing silymarin of the present invention preferably is achieved through the following technical solutions: the weight percentage by silymarin is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%.
Herba Silybi mariani prime system among the present invention by the fruit of feverfew Silybum Herba Silybi mariani through extracting the bulky powder of refining gained, English Silymarn by name.
Silymarin among the present invention can be according to the visible conventional method preparation of present document; Also can be by commercial direct acquisition.
Pharmaceutically acceptable carrier of the present invention can be any preparation Chinese medicinal granule pharmaceutically acceptable carrier commonly used or conventional, such as: 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 above-mentioned adjuvant function such as the diluent such as water, ethanol, polyvinylpyrrolidone (polyvidone), hydroxypropyl cellulose, Polyethylene Glycol (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, if can realize purpose of the present invention, also should be included in protection scope of the present invention.
The Chinese medicinal granule of containing silymarin of the present invention, 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 are united use.
The Chinese medicinal granule of containing silymarin of the present invention, described pharmaceutically acceptable carrier is preferably: crystalline cellulose element, micropowder silica gel, Polyethylene Glycol, Pulvis Talci, chitosan, Pulvis Talci, polyvidone.
The Chinese medicinal granule of containing silymarin of the present invention, described granule comprises master batch and the shell that is positioned on the master batch, and profile is that sphere or class are spherical, 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 Chinese medicinal granule of containing silymarin of the present invention, its particle diameter are 700～1500 μ m.
The Chinese medicinal granule of containing silymarin of the present invention, described granule also contains coating, and the weight of coating materials accounts for 2～5wt% of granule gross weight.
The Chinese medicinal granule of containing silymarin of the present invention 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 is prepared from pharmaceutically acceptable carrier, perhaps is prepared from by pharmaceutically acceptable carrier and corresponding silymarin dry powder.
The preparation method of the Chinese medicinal granule of containing silymarin of the present invention, step is as follows:
(1) it is an amount of that water intaking flies silibin;
(2) preparation of master batch: i. gets an amount of pharmaceutically acceptable carrier, the perhaps mixture of itself and silymarin dry powder, and crushing screening obtains the satisfactory material of granularity; Ii. get the material of a part of step I, drop in fluid bed side spray or the end spray pot, other gets it filled and learns acceptable carrier and/or silymarin and add water and be mixed with slurry, adopt fluid bed side spray or end pressure spray process to spray into, and sift out granule as parent nucleus, again parent nucleus is dropped in the pot, 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 silymarin is an amount of; Above-mentioned acceptable carrier is added in the above-mentioned silymarin, and it is for 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, makes spheroidal particle.
The preparation method of the Chinese medicinal granule of containing silymarin of the present invention, preferred steps is as follows:
(1) it is an amount of that water intaking flies silibin;
(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 silymarin 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 for subsequent use;
(3) preparation of product: get master batch 450g, the silymarin of 300g, with the silymarin weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with the silymarin weight ratio: the PVP-K30 weight ratio is 2: 5; Be formulated as the solution that concentration is 15wt% with dehydrated alcohol with a kind of in above-mentioned viscosity adjusting agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture, add in the silymarin, 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 simultaneously slurry and all spray into and make spheroidal particle.
In the preparation method of the Chinese medicinal granule of containing silymarin of the present invention, 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.
In the preparation method of the Chinese medicinal granule of containing silymarin of the present invention, No. 2 capsules of spheroidal particle fill that said method can be obtained, the 250mg/ grain is made capsule.
" setting of dosage form in the Chinese pharmacopoeia, and in order to distinguish different from 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 Chinese medicinal granule of containing silymarin of the present invention can also have coating outside it, 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 Chinese medicinal granule of containing silymarin of the present invention directly uses except can be used as common granule, can also be prepared into the dosage forms such as capsule as intermediate, as granule use etc., can be prepared in addition sustained-release preparation, positioning release medicine preparation etc.
The Chinese medicinal granule of containing silymarin of the present invention, 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 patient is that 0.1～4g gets final product each serving consumption generally, can reduce the fear that the patient takes medicine and produces 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 large, and (bulk density is 0.6～1.3g/ml), specific surface area is little (only has 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, weighed weight is put in the medicine sieve and is sieved.When sieving, will sieve and keep level, about come and go and sieve gently 3 minutes.Can not and can by granule and the powder summation of No. four sieves, must not cross 8.0% by a sieve.Granule of the present invention can not and can meet the pharmacopeia regulation by 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, 20 times of heating waters stirred 5 minutes, observed immediately.Soluble granule should all dissolve.
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, the 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 the 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 for explanation the present invention to the present invention without limits.
Embodiment 1
It is an amount of that water intaking flies silibin;
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 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% 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 for subsequent use at the master batch of 450 μ-600 μ to filter out particle diameter.
The preparation of product: get master batch 150g, microcrystalline Cellulose (200 order) 50g, polyethylene glycol 6000 (heating and melting) 80g, silymarin 720g; Microcrystalline Cellulose and micropowder silica gel are added in the silymarin, 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, be made into 7.5% coating solution with transparent coating material OPAGLOS 2 waters again, amount according to theory weightening finish 3% sprays into coating with coating solution, makes spheroidal particle.
Embodiment 2
It is an amount of that water intaking flies silibin;
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 and sprays 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 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 for subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 160g, microcrystalline Cellulose (200 order) 50g, micropowder silica gel 10g, silymarin 780g; Microcrystalline Cellulose and micropowder silica gel are added in the silymarin, and it is for 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 make spheroidal particle, be made into 7.5% coating solution with transparent coating material OPAGLOS 2 waters again, amount according to theory weightening finish 3% sprays into coating with coating solution, makes spheroidal particle.
Embodiment 3
It is an amount of that water intaking flies silibin;
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 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% 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 for subsequent use 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) 300g, silymarin 700g; Microcrystalline Cellulose and micropowder silica gel are added in the silymarin, 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, be made into 7.5% coating solution with transparent coating material OPAGLOS 2 waters again, 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 capsule.
Embodiment 4
It is an amount of that water intaking flies silibin;
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 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% 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 for subsequent use at the master batch of 300 μ～400 μ to filter out particle diameter.
The preparation of product: get master batch 1000g, add silymarin 1250g, 5% polyvidone solution, adding water, to mix into solid content be that 30% suspension is for 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 make spheroidal particle, be made into 7.5% coating solution with transparent coating material OPAGLOS 2 waters again, amount according to theory weightening finish 3% sprays into coating with coating solution, makes spheroidal particle.
Embodiment 5
It is an amount of that water intaking flies silibin;
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 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% 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 for subsequent use 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, silymarin 850g; Microcrystalline Cellulose and micropowder silica gel are added in the silymarin, and it is for 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 make spheroidal particle.
Embodiment 6
It is an amount of that water intaking flies silibin;
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-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 for subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 155g, microcrystalline Cellulose (200 order) 25g, micropowder silica gel 20g, silymarin 900g; Microcrystalline Cellulose and micropowder silica gel are added in the silymarin, and it is for 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 make spheroidal particle.
Embodiment 7
It is an amount of that water intaking flies silibin;
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 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% 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 for subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 200g, microcrystalline Cellulose (200 order) 300g, micropowder silica gel 100g, silymarin 400g; Microcrystalline Cellulose and micropowder silica gel are added in the silymarin, and it is for 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 make spheroidal particle.
Embodiment 8:
It is an amount of that water intaking flies silibin;
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% 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 for subsequent use at the master batch of 450～600 μ m to filter out particle diameter.
The selection of viscosity adjusting agent
A. get above-mentioned silymarin, 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 does not have complete film behind the liquid evaporation, 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 the characteristics such as powder, select the viscosity adjusting agent, experiment shows can select HPMC: PVP-K30 (2: 5) mixture as the viscosity adjusting agent, and also can select polyethylene glycol 6000 is the viscosity adjusting agent.
D. selection and silymarin weight ratio are 7: 25 HPMC: PVP-K30 (2: 5) mixture is the viscosity adjusting agent, perhaps selection and silymarin weight ratio are that 18: 25 polyethylene glycol 6000 is the viscosity adjusting agent, and material viscosity is increased to 16MPaS by 9.0MPaS.
The preparation of spheroidal particle of the present invention
A. get master batch 450g, with the silymarin weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC with the silymarin weight ratio: PVP-K30 (2: 5) mixture, the silymarin of 340g;
B. be formulated as the solution that concentration is 5wt% with dehydrated alcohol with a kind of in the above-mentioned viscosity adjusting agent, add in the silymarin, 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), 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 30 seconds.
With No. 2 capsules of spheroidal particle fill that obtain among the step c, the 250mg/ grain is made capsule.
Embodiment 9
It is an amount of that water intaking flies silibin.
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 silymarin (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 for subsequent use.
The preparation of product: get master batch 450g, the silymarin of 740g, with the silymarin weight ratio be 18: 25 polyethylene glycol 6000, with dehydrated alcohol above-mentioned viscosity adjusting agent polyethylene glycol 6000 is formulated as the solution that concentration is 15wt%, add in the silymarin, 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 simultaneously slurry and all spray into and make spheroidal particle.
Embodiment 10
It is an amount of that water intaking flies silibin;
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 silymarin (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 for subsequent use.
The preparation of product: get master batch 250g, the silymarin of 500g, with the silymarin weight ratio be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC: the PVP-K30 weight ratio is 2: 5; With dehydrated alcohol above-mentioned viscosity adjusting agent HPMC and PVP-K30 mixture are formulated as the solution that concentration is 15wt%, add in the silymarin, 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 simultaneously slurry and all spray into and make spheroidal particle.
Embodiment 11
It is an amount of that water intaking flies silibin;
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 silymarin (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 for subsequent use.
The preparation of product: get master batch 500g, the silymarin of 500g, with the silymarin weight ratio be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC: the PVP-K30 weight ratio is 2: 5; With dehydrated alcohol above-mentioned viscosity adjusting agent HPMC and PVP-K30 mixture are formulated as the solution that concentration is 15wt%, add in the silymarin, 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 simultaneously slurry and all spray into and make spheroidal particle.
Embodiment 12
It is an amount of that water intaking flies silibin;
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 silymarin (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 for subsequent use.
The preparation of product: get master batch 450g, the silymarin of 300g, with the silymarin weight ratio be 18: 25 polyethylene glycol 6000, with dehydrated alcohol above-mentioned viscosity adjusting agent polyethylene glycol 6000 is formulated as the solution that concentration is 15wt%, add in the silymarin, 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 simultaneously slurry and all spray into and make spheroidal particle.
Embodiment 13
It is an amount of that water intaking flies silibin;
The 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 silymarin 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 for subsequent use;
The preparation of product: get master batch 450g, the silymarin of 600g, with the silymarin weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with the silymarin weight ratio: the PVP-K30 weight ratio is 2: 5; Be formulated as the solution that concentration is 15wt% with dehydrated alcohol with a kind of in above-mentioned viscosity adjusting agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture, add in the silymarin, 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 simultaneously slurry and all spray into and make spheroidal particle.
Claims (5)
1. the preparation method of the Chinese medicinal granule of a containing silymarin is characterized in that step is as follows:
(1) it is an amount of that water intaking flies silibin;
(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 silymarin 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 for subsequent use;
(3) preparation of product: get master batch 450g, the silymarin of 300g, with the silymarin weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture with the silymarin weight ratio, wherein the HPMC:PVP-K30 weight ratio is 2: 5; Be formulated as the solution that concentration is 15wt% with dehydrated alcohol with a kind of in above-mentioned viscosity adjusting agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture, add in the silymarin, 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 simultaneously slurry and all spray into and make spheroidal particle.
2. the preparation method of the Chinese medicinal granule of containing silymarin as claimed in claim 1, it is characterized in that described Herba Silybi mariani prime system by the fruit of feverfew Silybum Herba Silybi mariani through extracting the bulky powder of refining gained, English Silymarn by name.
3. the preparation method of the Chinese medicinal granule of containing silymarin as claimed in claim 1, it is characterized in that prepared granule comprises master batch and the shell that is positioned on the master batch, profile is that sphere or class are spherical, 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.
4. the preparation method of the Chinese medicinal granule of containing silymarin as claimed in claim 1 is characterized in that its particle diameter of prepared granule is 700～1500 μ m.
5. the preparation method of the Chinese medicinal granule of containing silymarin as claimed in claim 1 is characterized in that prepared granule also contains coating, and the weight of coating materials accounts for 2～5wt% of granule gross weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101503262A CN101439068B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing silymarin and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101503262A CN101439068B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing silymarin and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101439068A CN101439068A (en) | 2009-05-27 |
| CN101439068B true CN101439068B (en) | 2013-03-13 |
Family
ID=40723766
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007101503262A Active CN101439068B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing silymarin and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101439068B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102018700B (en) * | 2009-09-22 | 2014-10-22 | 上海生物医药公共技术服务公司 | Pharmaceutical preparation containing silymarin and preparation thereof |
-
2007
- 2007-11-22 CN CN2007101503262A patent/CN101439068B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN101439068A (en) | 2009-05-27 |
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 | |
| CN101439067B (en) | Chinese medicine granular containing ginseng extract and preparation method thereof | |
| CN101439135A (en) | Chinese medicine granule containing extract of grassleaved sweetflag rhizome and preparation method thereof | |
| CN101439068B (en) | Chinese medicine granule containing silymarin and preparation method thereof | |
| CN101439063B (en) | Chinese medicine granular formulation containing Chinese angelica extract and preparation method thereof | |
| CN101439041B (en) | Chinese medicine granule containing breviscapine 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 | |
| CN101439084B (en) | Chinese medicine granule containing agastache extract and preparation method thereof | |
| CN101439065B (en) | Chinese medicine granular containing notoginseng extract 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 | |
| CN101439086B (en) | Chinese medicine granule containing total phenolic acids in salvia root and preparation method thereof | |
| 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 | |
| CN101439105B (en) | Chinese medicine granule containing spina date seed 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 | ||
| C53 | Correction of patent for invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 300410 Tianjin City Hedong District of Beichen Puji Road No. 2 city of the modern Chinese Medicine Applicant 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 Applicant before: Tianjin Tianshili Pharmaceutical Co., Ltd. |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: TIANJIN TASLY PHARMACEUTICAL CO., LTD. TO: TASLY PHARMACEUTICAL GROUP CO., LTD. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: TIANJIN TIANSHI SHENGTE PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: TASLY PHARMACEUTICAL GROUP CO., LTD. Effective date: 20141126 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 300410 BEICHEN, TIANJIN TO: 300402 BEICHEN, TIANJIN |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20141126 Address after: 300402 No. 3 Jiangxi Road, Beichen District, Tianjin Patentee after: Tianjin Tasly sants Pharmaceutical Co. 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. |