CN105548406B - Brave coltfoal hepatitis B quality of the pharmaceutical preparations control method and preparation - Google Patents

Brave coltfoal hepatitis B quality of the pharmaceutical preparations control method and preparation Download PDF

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CN105548406B
CN105548406B CN201610038218.5A CN201610038218A CN105548406B CN 105548406 B CN105548406 B CN 105548406B CN 201610038218 A CN201610038218 A CN 201610038218A CN 105548406 B CN105548406 B CN 105548406B
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radix
thick paste
small
ant
preparation
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CN105548406A (en
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李兴惠
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Li Xinghui
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A61K36/195—Strobilanthes
    • A—HUMAN NECESSITIES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/233—Bupleurum
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
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    • A61K36/18—Magnoliophyta (angiosperms)
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    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • A—HUMAN NECESSITIES
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    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704—Polygonum, e.g. knotweed
    • A—HUMAN NECESSITIES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
    • A61K36/725—Ziziphus, e.g. jujube
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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Abstract

The invention discloses brave coltfoal hepatitis B quality of the pharmaceutical preparations control method and preparation.The tiger coltfoal hepatitis B preparation is made of following 11 taste Chinese medicine and optional pharmaceutic adjuvant：Giant knotweed, ant, radix bupleuri, oriental wormwood, Radix Isatidis, the fruit of Chinese wolfberry, radix astragali, pseudo-ginseng, Radix Salviae Miltiorrhizae, Schisandra chinensis, jujube, this method include the use of the step of high performance liquid chromatography A differentiates the medicinal material pseudo-ginseng in the brave coltfoal hepatitis B preparation and/or radix astragali or their index components.The method of the present invention has excellent methodology performance.

Description

Brave coltfoal hepatitis B quality of the pharmaceutical preparations control method and preparation
Technical field
The present invention relates to a kind of detection method of Chinese medicine composition for treating and preventing virus B hepatitis, belong to Chinese medicine and show Generationization field.
Background technology
The Chinese medicine composition tiger coltfoal hepatitis B preparation of virus B hepatitis is treated and prevented, in CN1299725C (China Patent No. ZL200410065020.3) disclosed in.A kind of wherein disclosed optimizing prescriptions are as follows：2.66 parts of giant knotweed, ant 1.15 Part, 1.33 parts of Radix Isatidis, 1 part of oriental wormwood, 0.67 part of radix astragali, 0.53 part of the fruit of Chinese wolfberry, 0.67 part of Radix Salviae Miltiorrhizae, 0.07 part of pseudo-ginseng, jujube 0.2 Part, 0.53 part of Schisandra chinensis, 0.53 part of radix bupleuri.
As the medicine of Clinical practice, safely, effectively, it is controllable be thirdly big core key element.Although made of above-mentioned prescription Preparation for many years and achieves excellent clinical efficacy in Clinical practice, and drug safety also has no bad record.However, With modernization of Chinese medicine process, medicine is evaluated, is monitored using excellent quality control method, be production firm and Drug Administration mechanism urgently expects.
Brave coltfoal hepatitis B preparation has a soothing liver and strengthening spleen, dampness removing heat-clearing, it is promoting blood circulation and removing blood stasis the effect of.For chronic hepatitis B category liver Strongly fragrant insufficiency of the spleen and humid-heat stagnation card, symptoms include：Side of body rib turgor pain, gastral cavity spleen abdominal distension, anorexia, four limbs burnout, urine color Huang etc..
Tiger coltfoal hepatitis B preparation of the invention is big with prescription.Regrettably, existing brave coltfoal hepatitis B preparation, including its piece Agent and capsule, carry out it method of quality monitoring multi-purpose detection means than lower level, such as the spirit such as thin-layered chromatography The relatively low method of quick property, this kind of method are difficult in adapt to the quality monitoring of big prescription Chinese medicine preparation as the present invention.
Therefore, the quality control method of sensitive and accurate suitable brave coltfoal hepatitis B preparation is developed, is still those skilled in the art Urgently expect.
The content of the invention
It is an object of the invention to provide a kind of quality control method of sensitive and accurate suitable brave coltfoal hepatitis B preparation.
The present invention is realized according to following manner：
In first aspect present invention, there is provided be a kind of method of brave coltfoal hepatitis B quality of the pharmaceutical preparations control, the tiger coltfoal hepatitis B Preparation is made of following 11 taste Chinese medicine and optional pharmaceutic adjuvant：Giant knotweed, ant, radix bupleuri, oriental wormwood, Radix Isatidis, the fruit of Chinese wolfberry, Huang Stilbene, pseudo-ginseng, Radix Salviae Miltiorrhizae, Schisandra chinensis, jujube, this method include the use of high performance liquid chromatography A in the brave coltfoal hepatitis B preparation The step of medicinal material pseudo-ginseng and/or radix astragali or their index components are differentiated.
The method according to the invention, wherein the tiger coltfoal hepatitis B preparation is tablet, capsule or granule.
The method according to the invention, wherein the medicinal material ratio for preparing the brave coltfoal hepatitis B preparation is：665 parts by weight of giant knotweed, 287.5 parts by weight of ant, 132.5 parts by weight of radix bupleuri, 250 parts by weight of oriental wormwood, 332.5 parts by weight of Radix Isatidis, 132.5 weight of the fruit of Chinese wolfberry Measure part, 167.5 parts by weight of radix astragali, 17.5 parts by weight of pseudo-ginseng, 167.5 parts by weight of Radix Salviae Miltiorrhizae, 132.5 parts by weight of Schisandra chinensis, jujube 50 Parts by weight.
The method according to the invention, wherein the index components of the pseudo-ginseng and/or radix astragali are to be selected from following one kind or more Kind：Notoginsenoside R, ginsenoside Rg1, ginsenoside Rb1, Astragaloside IV.
The method according to the invention, wherein used in being differentiated to medicinal material pseudo-ginseng and/or radix astragali or their index components High performance liquid chromatography A include the following steps：
(1) take brave coltfoal hepatitis B preparation appropriate, it is finely ground, 2g is taken, adds methanol 40ml, be ultrasonically treated (for example, power 400~ 600W, 35~45kHz of frequency；For example, power 500W, frequency 40kHz) 30~50 minutes (such as 40 minutes) (art technologies Known in personnel, it is ultrasonically treated the index components that are so that in preparation and is dissolved in solvent, therefore its intensity for being ultrasonically treated is not yet Need considered critical), let cool, filter, filtrate is evaporated, and residue adds water 30ml to make dissolving, filtration, the n-butanol of filtrate water saturation Shaking extraction 2 times, each 20ml, merges n-butanol liquid, is washed twice with strong ammonia solution, each 20ml, take n-butanol liquid water-bath It is evaporated, residue adds methanol 2ml to make dissolving, as test solution；
(2) notoginsenoside R reference substance, ginsenoside Rg1's reference substance, ginsenoside Rb1's reference substance, Astragaloside IV separately are taken Reference substance, adds methanol that the mixed solution that every 1ml respectively contains 70 μ g is made, as reference substance solution；
(3) shine《Pharmacopoeia of People's Republic of China》The annex page 36 of version one " VI D high performance liquid chromatographies of annex " in 2010 Contained method test, Huo Zhezhao《Pharmacopoeia of People's Republic of China》Version four in 2015 page 59 " 0512 high performance liquid chromatography " Contained method test, using octadecylsilane chemically bonded silica as filler；Using water as mobile phase A, using acetonitrile as Mobile phase B, press Regulation in following table carries out gradient elution, flow velocity 1ml/min, and column temperature is 35 DEG C, evaporative light scattering detector detection；
Time (min) Mobile phase A (%) Mobile phase B (%)
0~4 90 10
4~5 90→80 10→20
5~14 80 20
14~15 80→77 20→23
15~25 77 23
25~26 77→68 23→32
26~30 68 32
30~33 68→65 32→35
33~51 65→40 35→60
(4) it is accurate respectively to draw each 15 μ l of above two solution, liquid chromatograph is injected, records chromatogram, is compared for examination Product solution chromatogram and reference substance solution chromatogram.
The method according to the invention, wherein in the high performance liquid chromatography A, compares test solution chromatogram and control Product solution chromatogram, it is described if the chromatographic peak identical with correspondence reference substance retention time is presented respectively in test sample chromatography Medicinal material pseudo-ginseng and/or radix astragali or their index components discrimination tests in brave coltfoal hepatitis B preparation is qualified, otherwise unqualified.
The method according to the invention, it is still further comprised using high performance liquid chromatography B to the brave coltfoal hepatitis B preparation In medicinal material giant knotweed, Radix Salviae Miltiorrhizae, Schisandra chinensis, and/or oriental wormwood or their index components the step of being differentiated.
The method according to the invention, wherein the medicinal material giant knotweed, Radix Salviae Miltiorrhizae, Schisandra chinensis, and/or the index components of oriental wormwood are choosings From following one or more：Polygonin, tanshin polyphenolic acid B, schizandrin, schizandrin A and chlorogenic acid.
The method according to the invention, wherein to medicinal material giant knotweed, Radix Salviae Miltiorrhizae, Schisandra chinensis, and/or oriental wormwood or their index components Carry out differentiating that high performance liquid chromatography B used includes the following steps：
(1) take brave coltfoal hepatitis B preparation appropriate, it is finely ground, about 2g is taken, it is accurately weighed, put in conical flask with cover, precision adds dilute Ethanol 100ml, close plug is weighed to weigh, be heated to reflux 1 it is small when, let cool, then it is weighed weigh, add Diluted Alcohol to supply the weight of less loss, Shake up, filter, subsequent filtrate is taken, up to test solution；
(2) polygonin reference substance, tanshin polyphenolic acid B reference substance, schizandrin reference substance, schizandrin A reference substance and green are taken Ortho acid reference substance, adds methanol that the mixed solution that every 1ml respectively contains 80 μ g is made, as reference substance solution；
(3) shine《Pharmacopoeia of People's Republic of China》The annex page 36 of version one " VI D high performance liquid chromatographies of annex " in 2010 Contained method test, Huo Zhezhao《Pharmacopoeia of People's Republic of China》Version four in 2015 page 59 " 0512 high performance liquid chromatography " Contained method test, using octadecylsilane chemically bonded silica as filler；Using acetonitrile as mobile phase A, using 0.1% phosphoric acid solution as Mobile phase B, the regulation according to the form below carry out gradient elution；Flow velocity is 0.8ml per minute；Measure wavelength is 215nm；Column temperature is 30 ℃；
(4) it is accurate respectively to draw each 15 μ l of above two solution, liquid chromatograph is injected, records chromatogram, is compared for examination Product solution chromatogram and reference substance solution chromatogram.
The method according to the invention, wherein in the high performance liquid chromatography B, compares test solution chromatogram and control Product solution chromatogram, it is described if the chromatographic peak identical with correspondence reference substance retention time is presented respectively in test sample chromatography Medicinal material giant knotweed, Radix Salviae Miltiorrhizae, Schisandra chinensis, and/or oriental wormwood or their index components discrimination tests in brave coltfoal hepatitis B preparation is qualified, no It is then unqualified.
The method according to the invention, it is still further comprised using high performance liquid chromatography C to the brave coltfoal hepatitis B preparation Assay is carried out, which carries out for both the medicinal material giant knotweed used in preparation and Schisandra chinensis.
The high performance liquid chromatography C of the present invention comprises the following steps：
(1) shine《Pharmacopoeia of People's Republic of China》The annex page 36 of version one " VI D high performance liquid chromatographies of annex " in 2010 Institute's support method measure, Huo Zhezhao《Pharmacopoeia of People's Republic of China》Version four in 2015 page 59 " 0512 high performance liquid chromatography " Institute's support method measure；
(2) chromatographic condition and system suitability：Using octadecylsilane chemically bonded silica as filler；Using acetonitrile as stream Dynamic phase A, using 0.1% phosphoric acid solution as Mobile phase B, the regulation according to the form below carries out gradient elution；Flow velocity is 0.8ml per minute； Column temperature is 30 DEG C；Detection wavelength is 215nm；Theoretical cam curve must not calculate less than 3000 by polygonin；
Time (min) A (%) B (%)
0~8 23 77
8~9 23→30 77→70
9~19 30 70
19~20 30→73 70→27
20~30 73 27
30~31 73→23 27→77
(3) preparation of reference substance solution：Take schizandrin reference substance and polygonin reference substance appropriate respectively, precision claims It is fixed, add methanol that mixed reference substance solutions of every 1ml containing 15 μ g of schizandrin, 160 μ g of polygonin is made, to obtain the final product；
(4) preparation of test solution：Take brave coltfoal hepatitis B preparation, determine the average weight of every preparation, take it is appropriate (if Preparation is that capsule then refers to the built-in particle or powder of capsule, also known as content), it is finely ground；About 2g is taken, it is accurately weighed, put tool Fill in conical flask in, precision add Diluted Alcohol 100ml, close plug is weighed to weigh, be heated to reflux 1 it is small when, let cool, then it is weighed weigh, add Diluted Alcohol supplies the weight of less loss, shakes up, and filtration, takes subsequent filtrate, to obtain the final product；
(5) determination method：It is accurate respectively to draw reference substance solution and test solution each 5 μ l or 10 μ l, inject liquid chromatogram Instrument, measure calculate the amount of the giant knotweed that includes in terms of polygonin (C20H22O8) in every preparation, and/or comprising Schisandra chinensis with The amount of schizandrin (C24H32O7) meter.
It is well known that for assay, be need it is accurate weigh test sample, this point with discrimination test not Together.The above-mentioned assay the step of in (4), " average weight for determining every preparation ", can if the preparation is tablet Such mode of operation is similar to take：20 are taken, accurately weighed, finely ground, precision weighs about 2g；Or it can take similar In such mode of operation：This product 20 is taken, after removing coating, accurately weighed, finely ground, precision weighs about 2g；Or take it It determines the average weight of every preparation well known to a person skilled in the art mode, the average weight and the accurate about 2g weighed Sample can be used for final calculating；For coating tablet, removing coating can be with not removing coating.In above-mentioned assay The step of (4) in, " average weight for determining every preparation ", if the preparation is capsule, can take similar to this The mode of operation of sample：This product content under content uniformity item is taken, is mixed, it is finely ground, about 2g is taken, it is accurately weighed；Or take it It determines the average weight of every preparation well known to a person skilled in the art mode, the average weight and the accurate about 2g weighed Sample can be used for final calculating.
The method according to the invention, wherein the tiger coltfoal hepatitis B preparation is to be prepared by a method comprising the following steps to obtain 's：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into Relative density is the thick paste of 1.25~1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C))；The dregs of a decoction are dried, and are crushed, standby With；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into phase It is the thick paste of 1.25~1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)) to density, the dregs of a decoction are spare；
(4) the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned radix astragali are taken, add 70% ethanol Refluxing extraction three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycle ethanol, be concentrated into phase It is the thick paste of 1.25~1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)) to density, and above-mentioned thick paste merges, with ant Ant powder, Radix Notoginseng powder mix, and dry, and crush, sieving；
(5) preparation, such as tablet, capsule, granule etc. is made in mixture obtained by step (4).
The method according to the invention, wherein the tiger coltfoal hepatitis B preparation is tablet, during it is prepared used in 1000 tablets Medicinal material amount is：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Huang Stilbene 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g.
The method according to the invention, wherein the tiger coltfoal hepatitis B preparation is tablet, to prepare in terms of 1000, it is preparing step Suddenly it is by being carried out including following operation in (5)：Mixture obtained by step (4) is added into starch, microcrystalline cellulose, sulphur Sour calcium and magnesium stearate auxiliary materials and mixing, adds the aqueous solution granulation of 3% hydroxypropyl methylcellulose, 60 DEG C of drying, are pressed into 1000, appoint Selection of land carries out film coating, to obtain the final product.
The method according to the invention, wherein the tiger coltfoal hepatitis B preparation is capsule, it is prepared used in 2500 capsules Chinese medicine amount be：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, the fruit of Chinese wolfberry 132.5g, radix astragali 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g.
The method according to the invention, wherein the tiger coltfoal hepatitis B preparation is capsule, to prepare in terms of 2500, it is being prepared It is by being carried out including following operation in step (5)：Add starch to make into 500g in right amount in mixture obtained by step (4), mix It is even, load capsule, be made 2500, to obtain the final product.
Further, second aspect of the present invention provides a kind of brave coltfoal hepatitis B tablet, and in terms of every 1000, it is using following amount Chinese medicine be prepared：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, matrimony vine Sub- 132.5g, radix astragali 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g.
Brave coltfoal hepatitis B tablet according to a second aspect of the present invention, including starch, microcrystalline cellulose, calcium sulfate and stearic acid Magnesium.
Brave coltfoal hepatitis B tablet according to a second aspect of the present invention, wherein the amount of the starch in every is 30~300mg, such as 30 ~250mg, such as 30~200mg.
Brave coltfoal hepatitis B tablet according to a second aspect of the present invention, wherein the amount of the microcrystalline cellulose in every is 20~100mg, Such as 30~80mg, such as 40~70mg.
Brave coltfoal hepatitis B tablet according to a second aspect of the present invention, wherein the amount of the calcium sulfate in every is 20~100mg, such as 30~80mg, such as 30~60mg.
Brave coltfoal hepatitis B tablet according to a second aspect of the present invention, wherein the amount of the magnesium stearate in every is 5~20mg, such as 5~15mg, such as 8~15mg.
Brave coltfoal hepatitis B tablet according to a second aspect of the present invention, it is prepared by a method comprising the following steps to obtain：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into Relative density is the thick paste of 1.25~1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C))；The dregs of a decoction are dried, and are crushed, standby With；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into phase It is the thick paste of 1.25~1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)) to density, the dregs of a decoction are spare；
(4) the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned radix astragali are taken, add 70% ethanol Refluxing extraction three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycle ethanol, be concentrated into phase It is the thick paste of 1.25~1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)) to density, and above-mentioned thick paste merges, with ant Ant powder, Radix Notoginseng powder mix, and dry, and crush, sieving；
(5) mixture obtained by step (4) is added into starch, microcrystalline cellulose, calcium sulfate and magnesium stearate auxiliary materials and mixing, added 3% hydroxypropyl methylcellulose aqueous solution is pelletized, 60 DEG C of drying, is pressed into 1000, optionally carries out film coating (such as film-coating It is using hydroxypropyl methyl cellulose as base-material), to obtain the final product.
Capsule content uniformity inspection can refer to《Pharmacopoeia of People's Republic of China》" 0103 glue of page 6 of version four in 2015 In wafer "【Content uniformity】In method carry out；Weight differential inspection is taken to can refer to during tablet《People's Republic of China's medicine Allusion quotation》In 2015 version four page 3 " 0101 tablets "【Weight differential】In method carry out.These methods are all this area skills Known to art personnel.Any embodiment of either side of the present invention is combined with any embodiment with either side.
Embodiment
Embodiment 1：Prepare brave coltfoal hepatitis B tablet
【Prescription】：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, the fruit of Chinese wolfberry 132.5g, radix astragali 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g.
【Preparation method】：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into Relative density is the thick paste of 1.30 (50 DEG C)；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into phase It is spare to the thick paste that density is 1.30 (50 DEG C), the dregs of a decoction；
(4) the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned radix astragali are taken, add 70% ethanol Refluxing extraction three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycle ethanol, be concentrated into phase The thick paste that density is 1.30 (50 DEG C), and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) mixture obtained by step (4) is added into starch 90g, microcrystalline cellulose 60g, calcium sulfate 50g and magnesium stearate 12g auxiliary materials and mixings, add 3% hydroxypropyl methylcellulose aqueous solution to pelletize, and 60 DEG C of drying, are pressed into 1000, film coating (coating weight gain 3%, thin film coating material is the hydroxypropyl methyl cellulose aqueous dispersion of commercialization, to obtain the final product.
Embodiment 2：Prepare brave coltfoal hepatitis B tablet
【Prescription】：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, the fruit of Chinese wolfberry 132.5g, radix astragali 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g.
【Preparation method】：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into Relative density is the thick paste of 1.35 (50 DEG C)；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into phase It is spare to the thick paste that density is 1.25 (50 DEG C), the dregs of a decoction；
(4) the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned radix astragali are taken, add 70% ethanol Refluxing extraction three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycle ethanol, be concentrated into phase The thick paste that density is 1.35 (50 DEG C), and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) mixture obtained by step (4) is added into starch 200g, microcrystalline cellulose 40g, calcium sulfate 60g and magnesium stearate 8g auxiliary materials and mixings, add 3% hydroxypropyl methylcellulose aqueous solution to pelletize, and 60 DEG C of drying, are pressed into 1000, film coating (coating weight gain 3%, thin film coating material is the hydroxypropyl methyl cellulose aqueous dispersion of commercialization, to obtain the final product.
Embodiment 3：Prepare brave coltfoal hepatitis B tablet
【Prescription】：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, the fruit of Chinese wolfberry 132.5g, radix astragali 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g.
【Preparation method】：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into Relative density is the thick paste of 1.25 (50 DEG C)；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into phase It is spare to the thick paste that density is 1.35 (50 DEG C), the dregs of a decoction；
(4) the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned radix astragali are taken, add 70% ethanol Refluxing extraction three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycle ethanol, be concentrated into phase The thick paste that density is 1.25 (50 DEG C), and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) mixture obtained by step (4) is added into starch 30g, microcrystalline cellulose 70g, calcium sulfate 30g and magnesium stearate 15g auxiliary materials and mixings, add 3% hydroxypropyl methylcellulose aqueous solution to pelletize, and 60 DEG C of drying, are pressed into 1000, film coating (coating weight gain 3%, thin film coating material is the hydroxypropyl methyl cellulose aqueous dispersion of commercialization, to obtain the final product.
Embodiment 4：Prepare brave coltfoal hepatitis B tablet
【Prescription】：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, the fruit of Chinese wolfberry 132.5g, radix astragali 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g.
【Preparation method】：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into Relative density is the thick paste of 1.25 (50 DEG C)；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into phase It is spare to the thick paste that density is 1.35 (50 DEG C), the dregs of a decoction；
(4) the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned radix astragali are taken, add 70% ethanol Refluxing extraction three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycle ethanol, be concentrated into phase The thick paste that density is 1.25 (50 DEG C), and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) mixture obtained by step (4) is added starch 100g, microcrystalline cellulose 50g and magnesium stearate 15g to mix, added 3% hydroxypropyl methylcellulose aqueous solution is pelletized, and 60 DEG C of drying, are pressed into 1000, film coating (coating weight gain 3%, film coating material Material is the hydroxypropyl methyl cellulose aqueous dispersion of commercialization, to obtain the final product.
In order to avoid tablet during long-term storage the moisture absorption, wrap film clothing is very useful way, for Chinese medicine It is even more so for tablet, and it is coated the overall appearance that can improve medicament.By four batches of tablets of above-described embodiment 1-4 in room Warm relative humidity is placed March under conditions of being less than 60%, it is found that the tablet clothing layer of embodiment 1-3 is unchanged, and 4 tablet of embodiment Clothing layer but has obvious cracking.In the experiment of supplement, by slight changes in the formulation and technology of the tablet of embodiment 1-3, i.e., only Calcium sulfate is not added with, gained tablet also finds that these tablet clothing layers have obvious cracking after equally handling 3 months；And if will be real Slight changes in the formulation and technology of the tablet of example 4 are applied, that is, add calcium sulfate 30mg, gained tablet is also sent out after equally handling 3 months These existing tablet clothing layers are unchanged.This shows that it is beneficial that calcium sulfate is added in prescription.In addition, in the experiment of supplement, With reference to the formula and preparation method of above-described embodiment 1-4, different is only the hydroxypropyl methyl fiber that film-coating is changed to other models Plain aqueous dispersion, i.e.,WithThree, obtains 12 kinds of bags Garment piece agent；Gained tablet equally processing also finds these tablet clothing layers respectively itself and corresponding embodiment 1-4 tablets after 3 months Clothing layer situation of change is identical, such as equal with 3 kinds of tablets of gained clothing layer after processing in 3 months during 1 tablet of embodiment, 3 kinds of clothing layers of parcel It is unchanged, but have with 3 kinds of tablets of gained clothing layer after processing in 3 months during 4 tablet of embodiment, 3 kinds of clothing layers of parcel and significantly open Split.Therefore, in Tablets, addition calcium sulfate is beneficial, and above-mentioned benefit can not be able to from calcium sulfate property at all It is expected that.
Embodiment 5：Prepare giant knotweed containing capsule for treating hepatitis B agent
【Prescription】：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, the fruit of Chinese wolfberry 132.5g, radix astragali 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g.
【Preparation method】：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into Relative density is the thick paste of 1.30 (50 DEG C)；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into phase It is spare to the thick paste that density is 1.30 (50 DEG C), the dregs of a decoction；
(4) the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned radix astragali are taken, add 70% ethanol Refluxing extraction three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycle ethanol, be concentrated into phase The thick paste that density is 1.30 (50 DEG C), and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) add starch to make into 500g in right amount in mixture obtained by step (4), mix, load capsule, be made 2500, i.e., Obtain capsule.
Test example 1：
Using high performance liquid chromatography A to the medicinal material pseudo-ginseng in brave coltfoal hepatitis B preparation and radix astragali or their index components into Row differentiates that the index components of pseudo-ginseng and radix astragali are：Notoginsenoside R, ginsenoside Rg1, ginsenoside Rb1, Astragaloside IV.
The method according to the invention, wherein used in being differentiated to medicinal material pseudo-ginseng and/or radix astragali or their index components High performance liquid chromatography A include the following steps：
(1) take brave coltfoal hepatitis B preparation appropriate, it is finely ground, 2g is taken, adds methanol 40ml, is ultrasonically treated (power 500W, frequency 40kHz) 40 minutes, let cool, filter, filtrate is evaporated, and residue adds water 30ml to make dissolving, filtration, the n-butanol of filtrate water saturation Shaking extraction 2 times, each 20ml, merges n-butanol liquid, is washed twice with strong ammonia solution, each 20ml, take n-butanol liquid water-bath It is evaporated, residue adds methanol 2ml to make dissolving, as test solution；
(2) notoginsenoside R reference substance, ginsenoside Rg1's reference substance, ginsenoside Rb1's reference substance, Astragaloside IV separately are taken Reference substance, adds methanol that the mixed solution that every 1ml respectively contains 70 μ g is made, as reference substance solution；
(3) shine《Pharmacopoeia of People's Republic of China》The annex page 36 of version one " VI D high performance liquid chromatographies of annex " in 2010 Contained method test, Huo Zhezhao《Pharmacopoeia of People's Republic of China》Version four in 2015 page 59 " 0512 high performance liquid chromatography " Contained method test (it is well known that the HPLC methods of two pharmacopeia versions are general), with octadecylsilane chemically bonded silica For filler；Using water as mobile phase A, using acetonitrile as Mobile phase B, the regulation according to the form below carries out gradient elution, flow velocity 1ml/ Min, column temperature are 35 DEG C, evaporative light scattering detector detection；
Time (min) Mobile phase A (%) Mobile phase B (%)
0~4 90 10
4~5 90→80 10→20
5~14 80 20
14~15 80→77 20→23
15~25 77 23
25~26 77→68 23→32
26~30 68 32
30~33 68→65 32→35
33~51 65→40 35→60
(4) it is accurate respectively to draw each 15 μ l of above two solution, liquid chromatograph is injected, records chromatogram, is compared for examination Product solution chromatogram and reference substance solution chromatogram.
According to the method for this test example, each preparation of the gained of example 1 above -5 is checked.The results show that reference substance solution chromatography Separating degree in figure between four kinds of index components is all higher than 3, has excellent separating degree (it is well known that separating degree is more than 1.5 just It is generally satisfactory)；Separating degree in test solution chromatogram between four kinds of index components is all higher than 3, and each peak From the interference of other miscellaneous peaks；The retention time of four kinds of index components and reference substance solution chromatography in test solution chromatogram Respective index components are coincide in figure.For these results, usually, closed for the discrimination test of these samples Lattice.In addition, the inventors discovered that, in this test example, in the range of 15~25min maintain mobile phase A for 77% be it is necessary, it is no Then Ginsenoside Rg1 and Rb1 cannot obtain therebetween excellent separating effect, and separating degree is less than 1.2；Applicant Make efforts to attempt to use the published various HPLC methods of the prior art, cannot obtain excellent separated same with Astragaloside IV When, moreover it is possible to realize the excellent separated effect of Ginsenoside Rg1 and Rb1 therebetween, not only Astragaloside IV is by it Its miscellaneous peak is disturbed, and separating degree is less than 1.2 to Ginsenoside Rg1 and Rb1 therebetween.
Test example 2：
Using high performance liquid chromatography B to medicinal material giant knotweed, Radix Salviae Miltiorrhizae, Schisandra chinensis and the oriental wormwood in the brave coltfoal hepatitis B preparation Or their index components are differentiated, medicinal material giant knotweed, Radix Salviae Miltiorrhizae, Schisandra chinensis and the index components of oriental wormwood have：Polygonin, red phenol Sour B, schizandrin, schizandrin A and chlorogenic acid.
The method according to the invention, wherein to medicinal material giant knotweed, Radix Salviae Miltiorrhizae, Schisandra chinensis and oriental wormwood or their index components into Row differentiates that high performance liquid chromatography B used includes the following steps：
(1) take brave coltfoal hepatitis B preparation appropriate, it is finely ground, about 2g is taken, it is accurately weighed, put in conical flask with cover, precision adds dilute Ethanol 100ml, close plug is weighed to weigh, be heated to reflux 1 it is small when, let cool, then it is weighed weigh, add Diluted Alcohol to supply the weight of less loss, Shake up, filter, subsequent filtrate is taken, up to test solution；
(2) polygonin reference substance, tanshin polyphenolic acid B reference substance, schizandrin reference substance, schizandrin A reference substance and green are taken Ortho acid reference substance, adds methanol that the mixed solution that every 1ml respectively contains 80 μ g is made, as reference substance solution；
(3) shine《Pharmacopoeia of People's Republic of China》The annex page 36 of version one " VI D high performance liquid chromatographies of annex " in 2010 Contained method test, Huo Zhezhao《Pharmacopoeia of People's Republic of China》Version four in 2015 page 59 " 0512 high performance liquid chromatography " Contained method test, using octadecylsilane chemically bonded silica as filler；Using acetonitrile as mobile phase A, using 0.1% phosphoric acid solution as Mobile phase B, the regulation according to the form below carry out gradient elution；Flow velocity is 0.8ml per minute；Measure wavelength is 215nm；Column temperature is 30 ℃；
(4) it is accurate respectively to draw each 15 μ l of above two solution, liquid chromatograph is injected, records chromatogram, is compared for examination Product solution chromatogram and reference substance solution chromatogram.
According to the method for this test example, each preparation of the gained of example 1 above -5 is checked.The results show that reference substance solution chromatography Separating degree in figure between five kinds of index components is all higher than 3, has excellent separating degree；Five kinds of fingers in test solution chromatogram Separating degree between mark component is all higher than 3, and each peak is from the interference of other miscellaneous peaks；Five kinds in test solution chromatogram The retention time of index components is coincide with respective index components in reference substance solution chromatogram.For these results, Usually, it is qualified for the discrimination test of these samples.
In addition, the inventors discovered that, in this test example, fine change gradient elution program, all can not be by tanshin polyphenolic acid B Separated with both chlorogenic acids, such as the mobile phase A during 15-28min in upper table is changed to 25%, just can not be by tanshin polyphenolic acid B With both chlorogenic acids separating degree up to more than 1.5；Applicant makes efforts to attempt to use the published various HPLC sides of the prior art Method, cannot obtain the excellent separating degree more than 1.5 between tanshin polyphenolic acid B and chlorogenic acid, not to mention realize more than 3 separating degrees Effect.
Test example 3：
Assay is carried out to the brave coltfoal hepatitis B preparation using high performance liquid chromatography C, which is directed to preparation Both the middle medicinal material giant knotweed used and Schisandra chinensis carry out.
High performance liquid chromatography C comprises the following steps：
(1) shine《Pharmacopoeia of People's Republic of China》The annex page 36 of version one " VI D high performance liquid chromatographies of annex " in 2010 Institute's support method measure, Huo Zhezhao《Pharmacopoeia of People's Republic of China》Version four in 2015 page 59 " 0512 high performance liquid chromatography " Institute's support method measure；
(2) chromatographic condition and system suitability：Using octadecylsilane chemically bonded silica as filler；Using acetonitrile as stream Dynamic phase A, using 0.1% phosphoric acid solution as Mobile phase B, the regulation according to the form below carries out gradient elution；Flow velocity is 0.8ml per minute； Column temperature is 30 DEG C；Detection wavelength is 215nm；Theoretical cam curve must not calculate less than 3000 by polygonin；
(3) preparation of reference substance solution：Take schizandrin reference substance and polygonin reference substance appropriate respectively, precision claims It is fixed, add methanol that mixed reference substance solutions of every 1ml containing 15 μ g of schizandrin, 160 μ g of polygonin is made, to obtain the final product；
(4) preparation of test solution：Take brave coltfoal hepatitis B preparation, determine the average weight of every preparation, take it is appropriate (if Preparation is that capsule then refers to the built-in particle or powder of capsule, also known as content), it is finely ground；About 2g is taken, it is accurately weighed, put tool Fill in conical flask in, precision add Diluted Alcohol 100ml, close plug is weighed to weigh, be heated to reflux 1 it is small when, let cool, then it is weighed weigh, add Diluted Alcohol supplies the weight of less loss, shakes up, and filtration, takes subsequent filtrate, to obtain the final product；
(5) determination method：It is accurate respectively to draw reference substance solution and test solution each 5 μ l or 10 μ l, inject liquid chromatogram Instrument, measure calculate the amount of the giant knotweed that includes in terms of polygonin (C20H22O8) in every preparation, and/or comprising Schisandra chinensis with The amount of schizandrin (C24H32O7) meter.
In the gradient elution of above-mentioned high performance liquid chromatography C, schizandrin and polygonin can be real with other peaks Existing separating degree is more than 3 separating effect；However it has been found that trickle change elution program (such as will flow during 20~30min The situation that dynamic phase A73% is changed to 75%), will result in schizandrin (separating degree is less than 1.2) too busy to get away with impurity peaks point is sent out It is raw.Use other chromatographic conditions instead, such as using octadecylsilane chemically bonded silica as filler, with methanol-acetonitrile-water (30:10: 60) it is mobile phase, flow velocity 0.5ml/min, Detection wavelength 303nm, number of theoretical plate is calculated by polygonin peak should be not less than 2000 During such chromatographic condition, schizandrin and polygonin can not be obtained and can be separated with other peak separating degrees more than 1.5 Effect；In another example using octadecylsilane chemically bonded silica as filler, with acetonitrile-water (23:77) it is mobile phase, flow velocity 0.8ml/ Min, Detection wavelength 306nm, number of theoretical plate during chromatographic condition, can not be obtained as the calculating of polygonin peak should be not less than 3000 1.5 separating effect can be more than with other peak separating degrees by obtaining schizandrin and polygonin.
The above-mentioned assay the step of in (4), " average weight for determining every preparation ", if the preparation is piece Agent, then take such mode of operation：20 are taken, accurately weighed, finely ground, precision weighs about 2g.Every system is determined in this way The average weight of agent, the average weight and the accurate about 2g samples weighed can be used for finally calculating in every preparation polygonin and/ Or the content of schizandrin.For coating tablet, removing coating can be with not removing coating, without materially affect, this Coating need not be removed in experiment.The above-mentioned assay the step of in (4), " average weight for determining every preparation ", if institute It is capsule to state preparation, then takes such mode of operation：Content uniformity measure is carried out in advance, is then taken under content uniformity item This product content, mixes, finely ground, takes about 2g, accurately weighed；So determine every preparation average weight, the average weight with The about 2g samples that precision weighs can be used for finally calculating the content of polygonin and/or schizandrin in every preparation.
According to the method for this test example, -5 each preparation of gained of measure example 1 above.The results show that each of embodiment 1-4 In agent, every tablet containing giant knotweed in terms of polygonin (C20H22O8) in the range of 5.3~7.1mg, be all higher than 4.5mg/；Often Grain tablet containing Schisandra chinensis in terms of schizandrin (C24H32O7) in the range of 0.41~0.83mg, be all higher than 0.32mg/. In the capsule of embodiment 5, every capsule is calculated as 2.3mg containing giant knotweed with polygonin (C20H22O8), more than 1.4mg/；Often Grain capsule is calculated as 0.22mg containing Schisandra chinensis with schizandrin (C24H32O7), more than 0.13mg/.

Claims (4)

1. a kind of tiger coltfoal hepatitis B tablet, it is characterised in that it is prepared according to following manner：
Prescription：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Huang Stilbene 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g；
Preparation method：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into 50 DEG C When relative density be 1.30 thick paste；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, when being concentrated into 50 DEG C Relative density be 1.30 thick paste, the dregs of a decoction are spare；
(4) giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned are taken（3）In the dregs of a decoction, add 70% alcohol reflux extract Three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycles ethanol, phase when being concentrated into 50 DEG C The thick paste that density is 1.30, and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) it is mixture addition starch 90g, microcrystalline cellulose 60g, calcium sulfate 50g and magnesium stearate 12g obtained by step (4) is auxiliary Material mixes, and adds 3% hydroxypropyl methylcellulose aqueous solution to pelletize, and 60 DEG C of drying, are pressed into 1000, film coating, and coating weight gain 3% is thin Film coating material is the hydroxypropyl methyl cellulose aqueous dispersion Opadry 85F20694 of commercialization, to obtain the final product.
2. a kind of tiger coltfoal hepatitis B tablet, it is characterised in that it is prepared according to following manner：
Prescription：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Huang Stilbene 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g；
Preparation method：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into 50 DEG C When relative density be 1.35 thick paste；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, when being concentrated into 50 DEG C Relative density be 1.25 thick paste, the dregs of a decoction are spare；
(4) giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned are taken（3）In the dregs of a decoction, add 70% alcohol reflux extract Three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycles ethanol, phase when being concentrated into 50 DEG C The thick paste that density is 1.35, and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) it is mixture addition starch 200g, microcrystalline cellulose 40g, calcium sulfate 60g and magnesium stearate 8g obtained by step (4) is auxiliary Material mixes, and adds 3% hydroxypropyl methylcellulose aqueous solution to pelletize, and 60 DEG C of drying, are pressed into 1000, film coating, and coating weight gain 3% is thin Film coating material is the hydroxypropyl methyl cellulose aqueous dispersion Opadry 85F20694 of commercialization, to obtain the final product.
3. a kind of tiger coltfoal hepatitis B tablet, it is characterised in that it is prepared according to following manner：
Prescription：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Huang Stilbene 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g；
Preparation method：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into 50 DEG C When relative density be 1.25 thick paste；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, when being concentrated into 50 DEG C Relative density be 1.35 thick paste, the dregs of a decoction are spare；
(4) giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned are taken（3）In the dregs of a decoction, add 70% alcohol reflux extract Three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycles ethanol, phase when being concentrated into 50 DEG C The thick paste that density is 1.25, and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) it is mixture addition starch 30g, microcrystalline cellulose 70g, calcium sulfate 30g and magnesium stearate 15g obtained by step (4) is auxiliary Material mixes, and adds 3% hydroxypropyl methylcellulose aqueous solution to pelletize, and 60 DEG C of drying, are pressed into 1000, film coating, and coating weight gain 3% is thin Film coating material is the hydroxypropyl methyl cellulose aqueous dispersion Opadry 85F20694 of commercialization, to obtain the final product.
4. a kind of tiger coltfoal hepatitis B tablet, it is characterised in that it is prepared according to following manner：
Prescription：Giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Huang Stilbene 167.5g, pseudo-ginseng 17.5g, Radix Salviae Miltiorrhizae 167.5g, Schisandra chinensis 132.5g, jujube 50g；
Preparation method：
(1) fine powder is ground into 11 taste medicinal materials, pseudo-ginseng；
(2) ant remove impurity, cleaning, add water to cook twice, every time 1 it is small when, decocting liquid filtration, merging filtrate, is concentrated into 50 DEG C When relative density be 1.25 thick paste；The dregs of a decoction are dried, and are crushed, spare；
(3) radix astragali, the fruit of Chinese wolfberry, jujube add water to cook secondary, every time 1 it is small when, decocting liquid filtration, merging filtrate, when being concentrated into 50 DEG C Relative density be 1.35 thick paste, the dregs of a decoction are spare；
(4) giant knotweed, Radix Isatidis, oriental wormwood, Radix Salviae Miltiorrhizae, Schisandra chinensis, radix bupleuri and above-mentioned are taken（3）In the dregs of a decoction, add 70% alcohol reflux extract Three times, for the first time 1.5 it is small when, second and third time it is each 1 it is small when, merge extracting solution, filtering, recycles ethanol, phase when being concentrated into 50 DEG C The thick paste that density is 1.25, and above-mentioned thick paste are merged, mixes, dries with ant powder, Radix Notoginseng powder, crush, sieving；
(5) mixture obtained by step (4) is added into starch 100g, microcrystalline cellulose 50g, calcium sulfate 30g and magnesium stearate 15g Mix, add 3% hydroxypropyl methylcellulose aqueous solution to pelletize, 60 DEG C of drying, are pressed into 1000, film coating, coating weight gain 3%, film Coating material is the hydroxypropyl methyl cellulose aqueous dispersion Opadry 85F20694 of commercialization, to obtain the final product.
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