CN103690759A - Compound liquorice-fritillaria thunbergii-ammonium chloride medicinal composition and preparation method thereof - Google Patents
Compound liquorice-fritillaria thunbergii-ammonium chloride medicinal composition and preparation method thereof Download PDFInfo
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 title claims abstract description 132
- 239000000203 mixture Substances 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims description 75
- 150000001875 compounds Chemical class 0.000 title abstract description 11
- 235000019270 ammonium chloride Nutrition 0.000 claims abstract description 62
- 239000012530 fluid Substances 0.000 claims abstract description 45
- 239000000843 powder Substances 0.000 claims abstract description 35
- 239000003814 drug Substances 0.000 claims abstract description 30
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-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)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 WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 21
- 235000006753 Platycodon grandiflorum Nutrition 0.000 claims abstract description 4
- 239000002775 capsule Substances 0.000 claims abstract description 3
- 239000008187 granular material Substances 0.000 claims description 67
- 239000003826 tablet Substances 0.000 claims description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 56
- 238000001914 filtration Methods 0.000 claims description 51
- 241000202807 Glycyrrhiza Species 0.000 claims description 49
- -1 glycyrrhiza compound Chemical class 0.000 claims description 49
- 239000007788 liquid Substances 0.000 claims description 44
- 239000008194 pharmaceutical composition Substances 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 30
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 22
- 239000002244 precipitate Substances 0.000 claims description 20
- 239000011248 coating agent Substances 0.000 claims description 19
- 238000000576 coating method Methods 0.000 claims description 19
- 230000001476 alcoholic effect Effects 0.000 claims description 18
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 18
- 238000005325 percolation Methods 0.000 claims description 18
- 239000012047 saturated solution Substances 0.000 claims description 18
- 239000000725 suspension Substances 0.000 claims description 18
- 229940079593 drug Drugs 0.000 claims description 17
- 238000005469 granulation Methods 0.000 claims description 12
- 230000003179 granulation Effects 0.000 claims description 12
- 229920001353 Dextrin Polymers 0.000 claims description 11
- 239000004375 Dextrin Substances 0.000 claims description 11
- 229920002472 Starch Polymers 0.000 claims description 11
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 11
- 235000010216 calcium carbonate Nutrition 0.000 claims description 11
- 235000019425 dextrin Nutrition 0.000 claims description 11
- 239000008107 starch Substances 0.000 claims description 11
- 235000019698 starch Nutrition 0.000 claims description 11
- 239000007888 film coating Substances 0.000 claims description 10
- 238000009501 film coating Methods 0.000 claims description 10
- 239000007779 soft material Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- 238000004321 preservation Methods 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 238000001291 vacuum drying Methods 0.000 claims description 9
- 238000001704 evaporation Methods 0.000 claims description 7
- 230000008020 evaporation Effects 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
- 239000006228 supernatant Substances 0.000 claims description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 4
- 240000003582 Platycodon grandiflorus Species 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 238000010790 dilution Methods 0.000 claims description 3
- 239000012895 dilution Substances 0.000 claims description 3
- 238000002481 ethanol extraction Methods 0.000 claims description 3
- 238000005352 clarification Methods 0.000 claims description 2
- 239000000341 volatile oil Substances 0.000 abstract description 24
- 238000005516 engineering process Methods 0.000 abstract description 10
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 abstract description 3
- 229920000858 Cyclodextrin Polymers 0.000 abstract 2
- 239000001116 FEMA 4028 Substances 0.000 abstract 2
- 244000303040 Glycyrrhiza glabra Species 0.000 abstract 2
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 abstract 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract 2
- 229960004853 betadex Drugs 0.000 abstract 2
- 235000011477 liquorice Nutrition 0.000 abstract 2
- 239000010676 star anise oil Substances 0.000 abstract 2
- 241001547125 Fritillaria thunbergii Species 0.000 abstract 1
- 244000274050 Platycodon grandiflorum Species 0.000 abstract 1
- 241000208966 Polygala Species 0.000 abstract 1
- 238000005538 encapsulation Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000002994 raw material Substances 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 12
- 238000012360 testing method Methods 0.000 description 10
- 239000003094 microcapsule Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 6
- 238000013112 stability test Methods 0.000 description 6
- 238000003860 storage Methods 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 239000001685 glycyrrhizic acid Substances 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides a compound liquorice-fritillaria thunbergii-ammonium chloride medicinal composition. The medicinal composition comprises the following components: 0.48-1.2 parts by volume of polygala fluid extract, 0.32-0.8 part by volume of fritillaria thunbergii fluid extract, 0.48-1.2 parts by volume of platycodon grandiflorum fluid extract, 0.8-2 parts by volume of liquorice fluid extract, 0.035-0.08 part by volume of star anise oil, 0.32-0.8 part by weight of liquorice extract powder, 0.4-1 part by weight of ammonium chloride and 0.42-0.88 part by weight of beta-cyclodextrin, wherein an inclusion compound is made from star anise oil and beta-cyclodextrin, and the ratio of part by volume and part by weight part are of ml/g or L/kg. According to the compound liquorice-fritillaria thunbergii-ammonium chloride medicinal composition, volatile oil is produced into capsules by adopting a micro-encapsulation technology, volatilization of the volatile oil in producing and storing processes can be reduced, and the stability of the volatile oil can be reinforced, so that the medicine stability can be improved and industrial production can be realized.
Description
Technical field
The invention belongs to pharmaceutical field, relate to a kind of pharmaceutical composition and preparation method thereof, be specifically related to a kind of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition and preparation method thereof.
Background technology
Glycyrrhiza compound Bulbus Fritillariae Thunbergii voltoide has been widely used for many years, is mainly used in treating cough that acute and chronic bronchitis causes, expectoration etc., certainly the report of listing so far there are no untoward reaction.At present, glycyrrhiza compound Bulbus Fritillariae Thunbergii voltoide on market mainly adopts traditional tablet manufacturing technique to make, in this technique, the method that adopts dissolve with ethanol to spray into granule the effective ingredient (volatile oil) in prescription adds, because volatile oil has strong volatility, cause adopting the less stable of the glycyrrhiza compound Bulbus Fritillariae Thunbergii voltoide of this explained hereafter, especially in production and storage process, be subject to the impact of physical factor and cannot guarantee that the long-term stability of volatile oil component exists, when medicine arrives in patient's hands, the volatile oil that plaing induces sweat acts on is almost lost and is made a gift of to the greatest extent.In addition, the production technology of the glycyrrhiza compound Bulbus Fritillariae Thunbergii voltoide adopting at present focuses mostly in laboratory research, not yet realizes suitability for industrialized production.
Therefore, how to develop a kind of production technology that realizes the glycyrrhiza compound Bulbus Fritillariae Thunbergii voltoide of suitability for industrialized production, reduce the volatilization of volatile ingredient in production and storage process in glycyrrhiza compound Bulbus Fritillariae Thunbergii voltoide, improve the stability of medicine, become this area problem urgently to be resolved hurrily.
Summary of the invention
For the problems referred to above, one object of the present invention is to provide a kind of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition, this glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition adopts microcapsule technology that ethereal oil is made to microcapsule, can reduce the volatilization of ethereal oil in production and storage process, strengthen the stability of ethereal oil, thereby improved the stability of medicine, and can realize suitability for industrialized production.
Another object of the present invention is to provide a kind of preparation method of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition.
For achieving the above object, the invention provides a kind of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition, this pharmaceutical composition comprises:
Wherein, described Oleum Anisi Stellati and described beta-schardinger dextrin-form clathrate, and described parts by volume is ml/g or L/kg with the ratio of weight portion.
Further, described pharmaceutical composition comprises:
Preferably, described pharmaceutical composition comprises:
Further, described pharmaceutical composition is tablet, capsule or granule; Preferably, described pharmaceutical composition also comprises pharmaceutically acceptable adjuvant.
Further, described pharmaceutical composition is tablet; Preferably, described pharmaceutical composition also comprises:
Starch 1.36-7.9 weight portion film coating powder 0.2-0.48 weight portion
Dextrin 0.24-1.05 weight portion calcium carbonate 0.48-1.2 weight portion.
Further, the preparation method of described Radix Polygalae fluid extractum comprises the following steps:
Radix Polygalae powder is broken into 65 orders, use 60%(volume ratio) ethanol water make solvent, flood after 24 hours, the speed of dividing with 1-3ml/ is carried out percolation, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, the collection liquid of filtering, and at cryoconcentration below 60 ℃ to thick paste shape, the first liquid of filtering that adds initial preservation, mix, drip concentrated ammonia solution and make the micro-aobvious alkalescence of filtrate, and there is ammonia smelly, the preferred 25-28%(volume ratio that drips) it is 9-10 that concentrated ammonia solution makes the pH value of filtrate, then use 60%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 38-48%(volume ratio) fluid extract, standing, after clarification, filter and obtain described Radix Polygalae fluid extractum.
Further, the preparation method of described Bulbus Fritillariae Thunbergii fluid extract comprises the following steps:
Bulbus Fritillariae Thunbergii is ground into 24 orders, use 70%(volume ratio) ethanol water make solvent, flood after 18 hours, the speed of dividing with 1-3ml/ is carried out percolation, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, by the remaining liquid of filtering at low-temperature evaporation below 60 ℃ to thick paste shape, the first liquid of filtering that adds initial preservation, mix, add again 70%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 50-70%(volume ratio) fluid extract, mix, standing, after filtration, obtain described Bulbus Fritillariae Thunbergii fluid extract.
Further, the preparation method of described Radix Platycodonis fluidextract comprises the following steps:
Balloonflower powder is broken into 24 orders, use 55%(volume ratio) ethanol water make solvent, flood after 48 hours, the slow percolation of speed dividing with 1-3ml/, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, by the remaining liquid of filtering at low-temperature evaporation below 60 ℃ to thick paste shape, the first liquid of filtering that adds initial preservation, mix, add again 55%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 40-50%(volume ratio) fluid extract, mix, standing, after filtration, obtain described Radix Platycodonis fluidextract.
Further, the preparation method of described Radix Glycyrrhizae extractum powder comprises the following steps:
By Radix Glycyrrhizae extracting in water three times, each 2 hours, merge extractive liquid,, placed extracting solution to spend the night, and made extracting solution precipitation, then got supernatant concentration to thick paste shape, and crushed after being dried to 80 order, obtains described Radix Glycyrrhizae extractum powder.
Further, the preparation method of described Radix Glycyrrhizae fluidextract comprises the following steps:
(1) by Radix Glycyrrhizae extracting in water three times, each 2 hours, merge extractive liquid,, placed extracting solution to spend the night, and made extracting solution precipitation, then got supernatant concentration to thick paste shape, and crushed after being dried to 80 order, obtains described Radix Glycyrrhizae extractum powder;
(2) by described Radix Glycyrrhizae extractum powder, use 92%(volume ratio) ethanol extraction three times, merge extractive liquid,, reclaims ethanol, add suitable quantity of water and 92%(volume ratio) ethanol dilution to crude drug weight, making ethanol content is 20-25%(volume ratio) Radix Glycyrrhizae fluidextract.
Further, the method for described Oleum Anisi Stellati and beta-schardinger dextrin-formation clathrate comprises the following steps:
Getting Oleum Anisi Stellati adds ethanol and is mixed with 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, at 56-60 ℃, preferably at 60 ℃ by the water-soluble preparation β-CD of beta-schardinger dextrin-saturated solution, at 40 ℃, Oleum Anisi Stellati alcoholic solution is mixed with beta-schardinger dextrin-saturated solution, under 850 revs/min, stir and within 2 hours, obtain milky suspension, by described milky suspension at 2-6 ℃, preferred standing 24-36 hour at 4 ℃, preferably 24 hours, after filtration, obtain white precipitate, by described white precipitate dry 3-8 hour at 45 ℃, preferably described white precipitate is first dried to 2-3h in 45 ℃ of low-temperature vacuum drying baking ovens, make after most of moisture volatilization, then in 45 ℃ of heated-air circulation ovens, place 5h, obtain described Oleum Anisi Stellati clathrate.
The present invention further provides the preparation method of aforementioned pharmaceutical compositions, this preparation method comprises the following steps:
Step a: Radix Polygalae fluid extractum, Bulbus Fritillariae Thunbergii fluid extract, Radix Platycodonis fluidextract, Radix Glycyrrhizae fluidextract, Radix Glycyrrhizae extractum, ammonium chloride, calcium carbonate, starch and dextrin are mixed to granulation after mixing thoroughly, being dried;
Step b: Oleum Anisi Stellati is mixed with the granule that step a obtains with the clathrate of beta-schardinger dextrin-.
Further, described preparation method is further comprising the steps of:
The mixture obtaining to step b adds pharmaceutically acceptable adjuvant, after soft material processed, granulation, obtains wet granular, and at 60 ℃, dry described wet granular, obtains dry granule after the granulate that sieves, and described dry granule is carried out to tabletting, coating, makes tablet.
Compared with prior art, glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition provided by the invention and preparation method thereof has the following advantages:
One, the present invention adopts microcapsule technology (ethereal oil being about in compositions is made clathrate (microcapsule)) to prepare glycyrrhiza compound Bulbus Fritillariae Thunbergii voltoide compositions, improved significantly the physicochemical property of glycyrrhiza compound Bulbus Fritillariae Thunbergii voltoide, reduced the volatilization of Oleum Anisi Stellati in production and storage process, strengthened the stability of Oleum Anisi Stellati, thereby improved the stability of medicine, guaranteed the curative effect of medicine;
Two, the present invention adopts microcapsule technology to prepare glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition, has improved the dissolubility of insoluble drug, can cover stink and the zest of medicine (Oleum Anisi Stellati) simultaneously;
Three, the present invention adopts microcapsule technology to prepare the production technology of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition, and enclose mild condition, technique be simple, be easy to control, enclose productive rate is high, constant product quality, is conducive to realize industrialization.
The specific embodiment
Referring to specific embodiment, the present invention is described.It will be appreciated by those skilled in the art that these embodiment are only for the present invention is described, the scope that it does not limit the present invention in any way.
Experimental technique in following embodiment, if no special instructions, is conventional method.In following embodiment, medicinal raw material used, reagent material etc., if no special instructions, be commercially available purchase product.
embodiment 1glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 1
Raw material preparation:
The preparation of Bulbus Fritillariae Thunbergii fluid extract: Bulbus Fritillariae Thunbergii is ground into 24 orders, use 70%(volume ratio) ethanol water make solvent, flood after 18 hours, the speed of dividing with 1-3ml/ is carried out percolation, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, by the remaining liquid of filtering at low-temperature evaporation below 60 ℃ to thick paste shape, the first liquid of filtering that adds initial preservation, mix, add again 70%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 50-70%(volume ratio) fluid extract, mix, standing, after filtration, obtain Bulbus Fritillariae Thunbergii fluid extract.
The preparation of Radix Platycodonis fluidextract: balloonflower powder is broken into 24 orders, use 55%(volume ratio) ethanol water make solvent, flood after 48 hours, the slow percolation of speed with 1-3ml/min, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, by the remaining liquid of filtering at low-temperature evaporation below 60 ℃ to thick paste shape, the first liquid of filtering that adds initial preservation, mix, add again 55%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 40-50%(volume ratio) fluid extract, mix, standing, after filtration, obtain described Radix Platycodonis fluidextract,
The preparation of Radix Polygalae fluid extractum: Radix Polygalae powder is broken into 65 orders, use 60%(volume ratio) ethanol water make solvent, flood after 24 hours, speed with 1-3ml/min is slowly carried out percolation, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, the collection liquid of filtering, and at low-temperature evaporation below 60 ℃ to thick paste shape, the first filtrate that adds initial preservation, mix, dropping 25-28%(volume ratio) concentrated ammonia solution makes filtrate be micro-aobvious alkalescence (pH value is 9-10), and there is ammonia smelly, then use 60%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 38-48%(volume ratio) fluid extract, standing, after filtration, obtain described Radix Polygalae fluid extractum,
The preparation of Radix Glycyrrhizae extractum fine powder: by Radix Glycyrrhizae extracting in water three times (wherein add water to and flood Radix Glycyrrhizae), each 2 hours, merge extractive liquid,, extracting solution is placed and spent the night, make extracting solution precipitation, then get supernatant concentration to thick paste shape, crushed after being dried to 80 order, obtains Radix Glycyrrhizae extractum fine powder;
The preparation of Radix Glycyrrhizae fluidextract: by Radix Glycyrrhizae extracting in water three times, each 2 hours, merge extractive liquid,, extracting solution is placed and spent the night, make extracting solution precipitation, then get supernatant concentration to thick paste shape, obtain Radix Glycyrrhizae extractum, by Radix Glycyrrhizae extractum crushed after being dried to 80 order, then use 92%(volume ratio) ethanol extraction three times, merge extractive liquid,, reclaims ethanol, add suitable quantity of water and 92%(volume ratio) ethanol dilution to crude drug weight, making ethanol content is 20-25%(volume ratio) Radix Glycyrrhizae fluidextract.
The preparation of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet:
Step a: take 0.96L Radix Polygalae fluid extractum, 0.64L Bulbus Fritillariae Thunbergii fluid extract, 0.96L Radix Platycodonis fluidextract, 1.6L Radix Glycyrrhizae fluidextract, 0.64kg Radix Glycyrrhizae extractum fine powder, 0.8kg ammonium chloride, 0.96kg calcium carbonate, 7.9kg starch and 0.83kg dextrin, and mixed granulation after mixing thoroughly, being dried;
Step b: 0.07L Oleum Anisi Stellati is dissolved in ethanol, preparation 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, and at 60 ℃ by the water-soluble preparation β-CD of 0.42kg β-CD saturated solution, then at 40 ℃, the Oleum Anisi Stellati alcoholic solution of preparation is mixed with β-CD saturated solution, under 850r/min, stir and within 2 hours, obtain milky suspension, described milky suspension is standing 24 hours at 4 ℃, after filtration, obtain white precipitate, by described white precipitate at 45 ℃ of low-temperature vacuum drying baking oven (ZDF-15, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) dry 2-3h in, make after most of moisture volatilization, then 45 ℃ of heated-air circulation oven (GT-G-II, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) in, place 5h, obtain Oleum Anisi Stellati clathrate,
Step c: the Oleum Anisi Stellati clathrate obtaining in step b is mixed with the granule obtaining in step a, through soft material processed, granulate and (adopt oscillating granulator (YK-160, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing)) after, obtain wet granular, dry described wet granular at 60 ℃, sieve after granulate and obtain dry granule, described dry granule is mixed with 0.38kg film coating powder, adopt rotary tablet machine (ZPY-23E, Shanghai Jiangnan Pharmaceutical Machinary Co., Ltd) described dry granule is carried out to tabletting, and adopt high-efficiency coating machine (BG-80, king's pharmaceutical machine Equipment Limited, sea, Nanjing) described granule is carried out to coating, obtain glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 1.
embodiment 2glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 2
Raw material preparation:
Preparation method with reference to each raw material in embodiment 1.
The preparation of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet:
Step a: take 0.9L Radix Polygalae fluid extractum, 0.8L Bulbus Fritillariae Thunbergii fluid extract, 1.2L Radix Platycodonis fluidextract, 2L Radix Glycyrrhizae fluidextract, 0.64kg Radix Glycyrrhizae extractum fine powder, 0.8kg ammonium chloride, 1.1kg calcium carbonate, 7.9kg starch and 0.83kg dextrin, and mixed granulation after mixing thoroughly, being dried;
Step b: 0.07L Oleum Anisi Stellati is dissolved in ethanol, preparation 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, and at 60 ℃ by the water-soluble preparation β-CD of 0.56kg β-CD saturated solution, then at 40 ℃, the Oleum Anisi Stellati alcoholic solution of preparation is mixed with β-CD saturated solution, under 850r/min, stir and within 2 hours, obtain milky suspension, described milky suspension is standing 24 hours at 4 ℃, after filtration, obtain white precipitate, by described white precipitate at 45 ℃ of low-temperature vacuum drying baking oven (ZDF-15, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) dry 2-3h in, make after most of moisture volatilization, then 45 ℃ of heated-air circulation oven (GT-G-II, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) in, place 5h, obtain Oleum Anisi Stellati clathrate,
Step c: the Oleum Anisi Stellati clathrate obtaining in step b is mixed with the granule obtaining in step a, through soft material processed, granulate and (adopt oscillating granulator (YK-160, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing)) after, obtain wet granular, dry described wet granular at 60 ℃, sieve after granulate and obtain dry granule, described dry granule is mixed with 0.38kg film coating powder, adopt rotary tablet machine (ZPY-23E, Shanghai Jiangnan Pharmaceutical Machinary Co., Ltd) described dry granule is carried out to tabletting, and adopt high-efficiency coating machine (BG-80, king's pharmaceutical machine Equipment Limited, sea, Nanjing) described granule is carried out to coating, obtain glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 2.
embodiment 3glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 3
Raw material preparation:
Preparation method with reference to each raw material in embodiment 1.
The preparation of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet:
Step a: take 0.7L Radix Polygalae fluid extractum, 0.64L Bulbus Fritillariae Thunbergii fluid extract, 0.9L Radix Platycodonis fluidextract, 0.8L Radix Glycyrrhizae fluidextract, 0.4kg Radix Glycyrrhizae extractum fine powder, 0.5kg ammonium chloride, 1.2kg calcium carbonate, 7.9kg starch and 0.83kg dextrin, and mixed granulation after mixing thoroughly, being dried;
Step b: 0.04L Oleum Anisi Stellati is dissolved in ethanol, preparation 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, and at 60 ℃ by the water-soluble preparation β-CD of 0.44kg β-CD saturated solution, then at 40 ℃, the Oleum Anisi Stellati alcoholic solution of preparation is mixed with β-CD saturated solution, under 850r/min, stir and within 2 hours, obtain milky suspension, described milky suspension is standing 24 hours at 4 ℃, after filtration, obtain white precipitate, by described white precipitate at 45 ℃ of low-temperature vacuum drying baking oven (ZDF-15, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) dry 2-3h in, make after most of moisture volatilization, then 45 ℃ of heated-air circulation oven (GT-G-II, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) in, place 5h, obtain Oleum Anisi Stellati clathrate,
Step c: the Oleum Anisi Stellati clathrate obtaining in step b is mixed with the granule obtaining in step a, through soft material processed, granulate and (adopt oscillating granulator (YK-160, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing)) after, obtain wet granular, dry described wet granular at 60 ℃, sieve after granulate and obtain dry granule, described dry granule is mixed with 0.38kg film coating powder, adopt rotary tablet machine (ZPY-23E, Shanghai Jiangnan Pharmaceutical Machinary Co., Ltd) described dry granule is carried out to tabletting, and adopt high-efficiency coating machine (BG-80, king's pharmaceutical machine Equipment Limited, sea, Nanjing) described granule is carried out to coating, obtain glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 3.
embodiment 4glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 4
Raw material preparation:
Preparation method with reference to each raw material in embodiment 1.
The preparation of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet:
Step a: take 0.6L Radix Polygalae fluid extractum, 0.5L Bulbus Fritillariae Thunbergii fluid extract, 0.48L Radix Platycodonis fluidextract, 1.2L Radix Glycyrrhizae fluidextract, 0.8kg Radix Glycyrrhizae extractum fine powder, 0.7kg ammonium chloride, 0.84kg calcium carbonate, 6.92kg starch and 0.72kg dextrin, and mixed granulation after mixing thoroughly, being dried;
Step b: 0.05L Oleum Anisi Stellati is dissolved in ethanol, preparation 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, and at 60 ℃ by the water-soluble preparation β-CD of 0.55kg β-CD saturated solution, then at 40 ℃, the Oleum Anisi Stellati alcoholic solution of preparation is mixed with β-CD saturated solution, under 850r/min, stir and within 2 hours, obtain milky suspension, described milky suspension is standing 24.5 hours at 4 ℃, after filtration, obtain white precipitate, by described white precipitate at 45 ℃ of low-temperature vacuum drying baking oven (ZDF-15, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) dry 2-3h in, make after most of moisture volatilization, then 45 ℃ of heated-air circulation oven (GT-G-II, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) in, place 5h, obtain Oleum Anisi Stellati clathrate,
Step c: the Oleum Anisi Stellati clathrate obtaining in step b is mixed with the granule obtaining in step a, through soft material processed, granulate and (adopt oscillating granulator (YK-160, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing)) after, obtain wet granular, dry described wet granular at 60 ℃, sieve after granulate and obtain dry granule, described dry granule is mixed with 0.34kg film coating powder, adopt rotary tablet machine (ZPY-23E, Shanghai Jiangnan Pharmaceutical Machinary Co., Ltd) described dry granule is carried out to tabletting, and adopt high-efficiency coating machine (BG-80, king's pharmaceutical machine Equipment Limited, sea, Nanjing) described granule is carried out to coating, obtain glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 4.
embodiment 5glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 5
Raw material preparation:
Preparation method with reference to each raw material in embodiment 1.
The preparation of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet:
Step a: take 0.48L Radix Polygalae fluid extractum, 0.32L Bulbus Fritillariae Thunbergii fluid extract, 0.6L Radix Platycodonis fluidextract, 1L Radix Glycyrrhizae fluidextract, 0.32kg Radix Glycyrrhizae extractum fine powder, 0.4kg ammonium chloride, 0.48kg calcium carbonate, 1.36kg starch and 0.24kg dextrin, and mixed granulation after mixing thoroughly, being dried;
Step b: 0.035L Oleum Anisi Stellati is dissolved in ethanol, preparation 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, and at 60 ℃ by the water-soluble preparation β-CD of 0.8kg β-CD saturated solution, then at 40 ℃, the Oleum Anisi Stellati alcoholic solution of preparation is mixed with β-CD saturated solution, under 850r/min, stir and within 2 hours, obtain milky suspension, described milky suspension is standing 24.5 hours at 4 ℃, after filtration, obtain white precipitate, by described white precipitate at 45 ℃ of low-temperature vacuum drying baking oven (ZDF-15, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) dry 2-3h in, make after most of moisture volatilization, then 45 ℃ of heated-air circulation oven (GT-G-II, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) in, place 5h, obtain Oleum Anisi Stellati clathrate,
Step c: the Oleum Anisi Stellati clathrate obtaining in step b is mixed with the granule obtaining in step a, through soft material processed, granulate and (adopt oscillating granulator (YK-160, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing)) after, obtain wet granular, dry described wet granular at 60 ℃, sieve after granulate and obtain dry granule, described dry granule is mixed with 0.48kg film coating powder, adopt rotary tablet machine (ZPY-23E, Shanghai Jiangnan Pharmaceutical Machinary Co., Ltd) described dry granule is carried out to tabletting, and adopt high-efficiency coating machine (BG-80, king's pharmaceutical machine Equipment Limited, sea, Nanjing) described granule is carried out to coating, obtain glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 5.
embodiment 6glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 6
Raw material preparation:
Preparation method with reference to each raw material in embodiment 1.
The preparation of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet:
Step a: take 1.2L Radix Polygalae fluid extractum, 0.7L Bulbus Fritillariae Thunbergii fluid extract, 1L Radix Platycodonis fluidextract, 1.7L Radix Glycyrrhizae fluidextract, 0.8kg Radix Glycyrrhizae extractum fine powder, 1kg ammonium chloride, 0.6kg calcium carbonate, 7.35kg starch and 1.05kg dextrin, and mixed granulation after mixing thoroughly, being dried;
Step b: 0.08L Oleum Anisi Stellati is dissolved in ethanol, preparation 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, and at 60 ℃ by the water-soluble preparation β-CD of 0.88kg β-CD saturated solution, then at 40 ℃, the Oleum Anisi Stellati alcoholic solution of preparation is mixed with β-CD saturated solution, under 850r/min, stir and within 2 hours, obtain milky suspension, described milky suspension is standing 24 hours at 4 ℃, after filtration, obtain white precipitate, by described white precipitate at 45 ℃ of low-temperature vacuum drying baking oven (ZDF-15, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) dry 2-3h in, make after most of moisture volatilization, then 45 ℃ of heated-air circulation oven (GT-G-II, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) in, place 5h, obtain Oleum Anisi Stellati clathrate,
Step c: the Oleum Anisi Stellati clathrate obtaining in step b is mixed with the granule obtaining in step a, through soft material processed, granulate and (adopt oscillating granulator (YK-160, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing)) after, obtain wet granular, dry described wet granular at 60 ℃, sieve after granulate and obtain dry granule, described dry granule is mixed with 0.48kg film coating powder, adopt rotary tablet machine (ZPY-23E, Shanghai Jiangnan Pharmaceutical Machinary Co., Ltd) described dry granule is carried out to tabletting, and adopt high-efficiency coating machine (BG-80, king's pharmaceutical machine Equipment Limited, sea, Nanjing) described granule is carried out to coating, obtain glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 6.
embodiment 7glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 7
Raw material preparation:
Preparation method with reference to each raw material in embodiment 1.
The preparation of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet:
Step a: take 0.8L Radix Polygalae fluid extractum, 0.6L Bulbus Fritillariae Thunbergii fluid extract, 0.96L Radix Platycodonis fluidextract, 1.5L Radix Glycyrrhizae fluidextract, 0.5kg Radix Glycyrrhizae extractum fine powder, 0.7kg ammonium chloride, 0.96kg calcium carbonate, 4.5kg starch and 0.5kg dextrin, and mixed granulation after mixing thoroughly, being dried;
Step b: 0.07L Oleum Anisi Stellati is dissolved in ethanol, preparation 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, and at 60 ℃ by the water-soluble preparation β-CD of 0.77kg β-CD saturated solution, then at 40 ℃, the Oleum Anisi Stellati alcoholic solution of preparation is mixed with β-CD saturated solution, under 850r/min, stir and within 2 hours, obtain milky suspension, described milky suspension is standing 24 hours at 4 ℃, after filtration, obtain white precipitate, by described white precipitate at 45 ℃ of low-temperature vacuum drying baking oven (ZDF-15, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) dry 2-3h in, make after most of moisture volatilization, then 45 ℃ of heated-air circulation oven (GT-G-II, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing) in, place 5h, obtain Oleum Anisi Stellati clathrate,
Step c: the Oleum Anisi Stellati clathrate obtaining in step b is mixed with the granule obtaining in step a, through soft material processed, granulate and (adopt oscillating granulator (YK-160, Feilong Pharmaceutical Machinery Equipment Factory, Nanjing)) after, obtain wet granular, dry described wet granular at 60 ℃, sieve after granulate and obtain dry granule, described dry granule is mixed with 0.2kg film coating powder, adopt rotary tablet machine (ZPY-23E, Shanghai Jiangnan Pharmaceutical Machinary Co., Ltd) described dry granule is carried out to tabletting, and adopt high-efficiency coating machine (BG-80, king's pharmaceutical machine Equipment Limited, sea, Nanjing) described granule is carried out to coating, obtain glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet 7.
Yield, envelop rate and the comprehensive grading of the Oleum Anisi Stellati clathrate of preparing according to following formula calculating above-described embodiment 1-7, result of calculation is as shown in table 1.
Comprehensive grading=envelop rate * 80%+ clathrate yield * 20%
Oleum Anisi Stellati clathrate performance parameter in table 1 embodiment 1-7
As seen from Table 1, the envelop rate comprehensive grading of clathrate prepared by above-described embodiment 1-7 is all more than 81%, tablet product qualified rate is all greater than 80%, especially the comprehensive grading of the glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet of embodiment 3 and 7 preparations reaches more than 92%, the preparation method that shows glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet of the present invention meets 2010 editions two pertinent regulations of < < Chinese Pharmacopoeia > >, can meet actual production and industrialized needs.
comparative example
Adopt existing method to prepare glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet, wherein each amounts of components is identical with corresponding consumption in embodiment 1.Concrete preparation method is as follows:
Step 1: adopt the method for embodiment 1 to prepare Bulbus Fritillariae Thunbergii fluid extract, Radix Platycodonis fluidextract, Radix Polygalae fluid extractum, Radix Glycyrrhizae extractum fine powder, Radix Glycyrrhizae fluidextract;
Step 2: prepare granule according to the method in embodiment 1 step a;
Step 3: the granule of Oleum Anisi Stellati and step 2 preparation is mixed; after soft material processed, granulation, obtain wet granular; dry described wet granular at 60 ℃; sieve after granulate and obtain dry granule; described dry granule is mixed with 0.38kg film coating powder; adopt rotary tablet machine to carry out tabletting to described dry granule, and adopt high-efficiency coating machine to carry out coating to described granule, obtain glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet.
test 1: glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet performance test
Character observation: the glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet of preparing in above-described embodiment 1-7 is Film coated tablets, removes aobvious light brown after coating, and tablet is complete bright and clean, and color and luster is even, and hardness is moderate.
Medicine performance checking and mensuration: weight differential, disintegration, ammonium chloride and the glycyrrhizic acid content of the glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet of preparing according to the 4th detection embodiment 1-7 of the international national drug standards of chemical drugs Di Sheng, test result is as shown in table 2.
Table 2: the performance detection data of the glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet of preparing in embodiment 1-7
In above-mentioned table 2, the concrete meaning of each test item is as follows:
Differentiate that (1) represents: in test sample chromatograph, with the corresponding position of Radix Polygalae control medicinal material chromatograph on, the speckle of aobvious same color, is judged to up to specificationly, otherwise is judged to against regulation.
Differentiate that (2) represent: in test sample chromatograph, with the corresponding position of Bulbus Fritillariae Thunbergii control medicinal material chromatograph on, the speckle of aobvious same color, is judged to up to specificationly, otherwise is judged to against regulation.
Weight differential: be judged to up to specification in 0.6 ± 0.03g.
Disintegration: if all disintegrates within 60 minutes are judged to up to specification.
Ammonium chloride content %: refer to that the actual content of ammonium chloride in tablet accounts for the ratio of ammonium chloride theoretical content.
As seen from Table 2, the related request during the national drug standards that all meet the glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet that adopts the inventive method to prepare detect.
test 2: clathrate stability test
According to < < Chinese Pharmacopoeia > > version determination of volatile oil method in 2010, under the condition that Oleum Anisi Stellati clathrate prepared by above-described embodiment 1-7 is 70-80% at 38-42 ℃, relative humidity, carry out oil content detection, test respectively the oil content (Fructus Anisi Stellati weight of oil account for the percentage ratio of clathrate weight) of Oleum Anisi Stellati clathrate 1,2,3, after June.
Table 3: embodiment of the present invention 1-7 volatile oil stability test
As seen from Table 3, after high temperature experiment, 1,2,3, after June, all there is not significant change in the Fructus Anisi Stellati oil content that adopts clathrate in glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet prepared by the inventive method, illustrate that thus the present invention adopts glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet prepared by clathrate process can improve the stability of volatile oil, extend volatile oil retention time, thereby can improve the stability of medicine.
test 3: volatile oil stability test in medicament
Respectively under high temperature and room temperature, investigate the stability of glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet prepared by above-described embodiment 1-7 and comparative example.High temperature test condition is as follows: under the condition that is 60 ± 10% at relative humidity, above-mentioned glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet is placed 10 days in 40 ℃ and 60 ℃ of calorstats, interval different time sampling, by 2005 editions one appendix XD determination of volatile oil Division A League Matches of French Football method of < < Chinese Pharmacopoeia > > (57 pages of appendix), measure volatile oil content (take ml/100g sample as unit), measurement result is as shown in table 4 and table 5.Room temperature test condition is as follows: under the condition that is 60 ± 10% at relative humidity, above-mentioned glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet is placed 3 months at 25 ± 2 ℃, interval different time sampling, by 2005 editions one appendix XD determination of volatile oil Division A League Matches of French Football method of < < Chinese Pharmacopoeia > > (57 pages of appendix), measure volatile oil content (take ml/100g sample as unit), measurement result is as shown in table 6.
Volatile oil stability test in medicament at table 440 ℃
Volatile oil stability test in medicament at table 560 ℃
Volatile oil stability test in medicament under table 6 room temperature
From table 4 to table 6, find out, when glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet prepared by the embodiment of the present invention is placed under high temperature (40 ℃, 60 ℃) and room temperature, in tablet, Fructus Anisi Stellati oil content remains unchanged substantially, and while adopting glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet prepared by existing method to place under high temperature (40 ℃, 60 ℃) and room temperature, in tablet, Fructus Anisi Stellati oil content reduces gradually.Explanation thus, with respect to prior art, the present invention adopts microcapsule technology to prepare glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride tablet, is conducive to improve the stability of volatile oil, thereby has improved the stability of medicine.
Specific description of embodiments of the present invention above does not limit the present invention, and those skilled in the art can make according to the present invention various changes or distortion, only otherwise depart from spirit of the present invention, all should belong to the scope of claims of the present invention.
Claims (12)
1. a glycyrrhiza compound Bulbus Fritillariae Thunbergii ammonium chloride pharmaceutical composition, this pharmaceutical composition comprises:
Wherein, described Oleum Anisi Stellati and described beta-schardinger dextrin-form clathrate, and described parts by volume is ml/g or L/kg with the ratio of weight portion.
2. pharmaceutical composition according to claim 1, is characterized in that, described pharmaceutical composition comprises:
Preferably, described pharmaceutical composition comprises:
3. pharmaceutical composition according to claim 1 and 2, is characterized in that, described pharmaceutical composition is tablet, capsule or granule; Preferably, described pharmaceutical composition also comprises pharmaceutically acceptable adjuvant.
4. according to the pharmaceutical composition described in any one in claims 1 to 3, it is characterized in that, described pharmaceutical composition is tablet; Preferably, described pharmaceutical composition also comprises:
Starch 1.36-7.9 weight portion film coating powder 0.2-0.48 weight portion
Dextrin 0.24-1.05 weight portion calcium carbonate 0.48-1.2 weight portion.
5. according to the pharmaceutical composition described in any one in claim 1 to 4, it is characterized in that, the preparation method of described Radix Polygalae fluid extractum comprises the following steps:
Radix Polygalae powder is broken into 65 orders, use 60%(volume ratio) ethanol water make solvent, flood after 24 hours, the speed of dividing with 1-3ml/ is carried out percolation, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, the collection liquid of filtering, and at cryoconcentration below 60 ℃ to thick paste shape, the first liquid of filtering that adds initial preservation, mix, drip concentrated ammonia solution and make the micro-aobvious alkalescence of filtrate, and there is ammonia smelly, the preferred 25-28%(volume ratio that drips) it is 9-10 that concentrated ammonia solution makes the pH value of filtrate, then use 60%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 38-48%(volume ratio) fluid extract, standing, after clarification, filter and obtain described Radix Polygalae fluid extractum.
6. according to the pharmaceutical composition described in any one in claim 1 to 5, it is characterized in that, the preparation method of described Bulbus Fritillariae Thunbergii fluid extract comprises the following steps:
Bulbus Fritillariae Thunbergii is ground into 24 orders, use 70%(volume ratio) ethanol water make solvent, flood after 18 hours, the speed of dividing with 1-3ml/ is carried out percolation, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, by the remaining liquid of filtering at low-temperature evaporation below 60 ℃ to thick paste shape, the first liquid of filtering that adds initial preservation, mix, add again 70%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 50-70%(volume ratio) fluid extract, mix, standing, after filtration, obtain described Bulbus Fritillariae Thunbergii fluid extract.
7. according to the pharmaceutical composition described in any one in claim 1 to 6, it is characterized in that, the preparation method of described Radix Platycodonis fluidextract comprises the following steps:
Balloonflower powder is broken into 24 orders, use 55%(volume ratio) ethanol water make solvent, flood after 48 hours, the slow percolation of speed dividing with 1-3ml/, collect 85% the first liquid of filtering, another extracting container is preserved the liquid of just filtering, continue percolation, after soluble component is filtered out completely, by the remaining liquid of filtering at low-temperature evaporation below 60 ℃ to thick paste shape, the first liquid of filtering that adds initial preservation, mix, add again 55%(volume ratio) ethanol water be diluted to crude drug weight, making ethanol content is 40-50%(volume ratio) fluid extract, mix, standing, after filtration, obtain described Radix Platycodonis fluidextract.
8. according to the pharmaceutical composition described in any one in claim 1 to 7, it is characterized in that, the preparation method of described Radix Glycyrrhizae extractum powder comprises the following steps:
By Radix Glycyrrhizae extracting in water three times, each 2 hours, merge extractive liquid,, placed extracting solution to spend the night, and made extracting solution precipitation, then got supernatant concentration to thick paste shape, and crushed after being dried to 80 order, obtains described Radix Glycyrrhizae extractum powder.
9. according to the pharmaceutical composition described in any one in claim 1 to 8, it is characterized in that, the preparation method of described Radix Glycyrrhizae fluidextract comprises the following steps:
(1) by Radix Glycyrrhizae extracting in water three times, each 2 hours, merge extractive liquid,, placed extracting solution to spend the night, and made extracting solution precipitation, then got supernatant concentration to thick paste shape, and crushed after being dried to 80 order, obtains described Radix Glycyrrhizae extractum powder;
(2) by described Radix Glycyrrhizae extractum powder, use 92%(volume ratio) ethanol extraction three times, merge extractive liquid,, reclaims ethanol, add suitable quantity of water and 92%(volume ratio) ethanol dilution to crude drug weight, making ethanol content is 20-25%(volume ratio) Radix Glycyrrhizae fluidextract.
10. according to the pharmaceutical composition described in any one in claim 1 to 9, it is characterized in that, the method that described Oleum Anisi Stellati and beta-schardinger dextrin-form clathrate comprises the following steps:
Getting Oleum Anisi Stellati adds ethanol and is mixed with 65%(volume ratio) Oleum Anisi Stellati alcoholic solution, at 56-60 ℃, preferably at 60 ℃ by the water-soluble preparation β-CD of beta-schardinger dextrin-saturated solution, at 40 ℃, Oleum Anisi Stellati alcoholic solution is mixed with beta-schardinger dextrin-saturated solution, under 850 revs/min, stir and within 2 hours, obtain milky suspension, by described milky suspension at 2-6 ℃, preferred standing 24-36 hour at 4 ℃, preferably 24 hours, after filtration, obtain white precipitate, by described white precipitate dry 3-8 hour at 45 ℃, preferably described white precipitate is first dried to 2-3h in 45 ℃ of low-temperature vacuum drying baking ovens, make after most of moisture volatilization, then in 45 ℃ of heated-air circulation ovens, place 5h, obtain described Oleum Anisi Stellati clathrate.
11. according to the preparation method of the pharmaceutical composition described in any one in claim 1 to 10, and this preparation method comprises the following steps:
Step a: Radix Polygalae fluid extractum, Bulbus Fritillariae Thunbergii fluid extract, Radix Platycodonis fluidextract, Radix Glycyrrhizae fluidextract, Radix Glycyrrhizae extractum, ammonium chloride, calcium carbonate, starch and dextrin are mixed to granulation after mixing thoroughly, being dried;
Step b: Oleum Anisi Stellati is mixed with the granule that step a obtains with the clathrate of beta-schardinger dextrin-.
12. preparation methoies according to claim 11, is characterized in that, described preparation method is further comprising the steps of:
The mixture obtaining to step b adds pharmaceutically acceptable adjuvant, after soft material processed, granulation, obtains wet granular, and at 60 ℃, dry described wet granular, obtains dry granule after the granulate that sieves, and described dry granule is carried out to tabletting, coating, makes tablet.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115372501A (en) * | 2022-07-27 | 2022-11-22 | 广州科曼生物科技有限公司 | Thunberg fritillary bulb or Hubei fritillary bulb contrast extract and preparation method and application thereof |
| CN115372501B (en) * | 2022-07-27 | 2024-03-26 | 广州科曼生物科技有限公司 | Control extract of fritillaria thunbergii or fritillaria hubei, preparation method and application thereof |
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