CN105548406A - Quality control method for Huju hepatitis B preparation and preparation - Google Patents

Quality control method for Huju hepatitis B preparation and preparation Download PDF

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CN105548406A
CN105548406A CN201610038218.5A CN201610038218A CN105548406A CN 105548406 A CN105548406 A CN 105548406A CN 201610038218 A CN201610038218 A CN 201610038218A CN 105548406 A CN105548406 A CN 105548406A
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preparation
hepatitis
fruit
coltfoal
reference substance
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CN105548406B (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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    • A61K36/00—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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/233—Bupleurum
    • A—HUMAN NECESSITIES
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    • 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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
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    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
    • 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)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A61K36/315—Isatis, e.g. Dyer's woad
    • 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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • 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)
    • A61K36/57—Magnoliaceae (Magnolia family)
    • 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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    • A61K36/185—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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    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • 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, decoction
    • A—HUMAN NECESSITIES
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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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    • 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
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Abstract

The invention discloses a quality control method for a Huju hepatitis B preparation and the preparation. The Huju hepatitis B preparation is prepared from the following 11 traditional Chinese medicines and an optional pharmaceutical adjuvant: polygonum cuspidatum, ants, radix bupleuri, herba artemisiae scopariae, radix isatidis, barbary wolfberry fruit, radix astragali, panax notoginseng, salviae miltiorrhizae, fructus schizandrae and jujubes. The quality control method comprises a step of using a high performance liquid chromatography A to identify the medicinal materials panax notoginseng and/or radix astragali or index components of the both in the Huju hepatitis B preparation. The method disclosed by the invention is excellent in methodological performance.

Description

Tiger coltfoal hepatitis B quality of the pharmaceutical preparations control method and preparation
Technical field
The present invention relates to the detection method of Chinese medicine composition of a kind for the treatment of and prevention virus B hepatitis, belong to modern Chinese traditional medicine field.
Background technology
The Chinese medicine composition tiger coltfoal hepatitis B preparation for the treatment of and prevention virus B hepatitis, open in CN1299725C (China Patent No. ZL200410065020.3).Disclosed in it, a kind of optimizing prescriptions is as follows: giant knotweed 2.66 parts, ant 1.15 parts, Radix Isatidis 1.33 parts, oriental wormwood 1 part, the Radix Astragali 0.67 part, the fruit of Chinese wolfberry 0.53 part, the red sage root 0.67 part, pseudo-ginseng 0.07 part, 0.2 part, date, 0.53 part, the fruit of Chinese magnoliavine, radix bupleuri 0.53 part.
As the medicine of Clinical practice, safe, effective, controlled is its three macronucleus key element.Although the preparation be made up of above-mentioned prescription at Clinical practice for many years and achieve excellent clinical efficacy, and drug safety also has no bad record.But along with modernization of Chinese medicine process, using excellent quality control method to evaluate medicine, monitor, is that production firm and Drug Administration mechanism urgently expect.
Tiger coltfoal hepatitis B preparation has soothing liver and strengthening spleen, dampness removing heat-clearing, effect promoting blood circulation and removing blood stasis.Belong to stagnation of liver-QI with deficiency of the spleen for chronic hepatitis B to hold concurrently humid-heat stagnation card, disease is seen: side of body rib turgor pain, gastral cavity spleen abdominal distension, anorexia, and four limbs burnout, urine look yellow.
It is large that the present invention tiger coltfoal hepatitis B preparation has prescription.Regrettably, existing brave coltfoal hepatitis B preparation, comprise its Tablet and Capsula agent, it is carried out to the method multiplex more rudimentary detection means of quality monitoring, the method that the sensitivitys such as such as thin-layered chromatography are relatively low, these class methods are difficult to the quality monitoring adapting to the so large prescription Chinese medicine preparation of the present invention.
Therefore, develop the quality control method of sensitive and accurate applicable brave coltfoal hepatitis B preparation, be still that those skilled in the art urgently expect.
Summary of the invention
The object of the present invention is to provide a kind of quality control method of sensitive and accurate applicable brave coltfoal hepatitis B preparation.
The present invention is according to such as under type realization:
In first aspect present invention, provide a kind of method that brave coltfoal hepatitis B quality of the pharmaceutical preparations controls, described brave coltfoal hepatitis B preparation is made up of following 11 taste Chinese medicines and optional pharmaceutic adjuvant: giant knotweed, ant, radix bupleuri, oriental wormwood, Radix Isatidis, the fruit of Chinese wolfberry, the Radix Astragali, pseudo-ginseng, the red sage root, the fruit of Chinese magnoliavine, date, and the method comprises the step using high performance liquid chromatography A to differentiate the medicinal material pseudo-ginseng in described brave coltfoal hepatitis B preparation and/or the Radix Astragali or their index components.
According to method of the present invention, wherein said brave coltfoal hepatitis B preparation is tablet, capsule or granule.
According to method of the present invention, the medicinal material ratio wherein preparing described brave coltfoal hepatitis B preparation is: giant knotweed 665 weight portion, ant 287.5 weight portion, radix bupleuri 132.5 weight portion, oriental wormwood 250 weight portion, Radix Isatidis 332.5 weight portion, the fruit of Chinese wolfberry 132.5 weight portion, the Radix Astragali 167.5 weight portion, pseudo-ginseng 17.5 weight portion, the red sage root 167.5 weight portion, the fruit of Chinese magnoliavine 132.5 weight portion, date 50 weight portion.
According to method of the present invention, the index components of wherein said pseudo-ginseng and/or the Radix Astragali is selected from following one or more: notoginsenoside R, ginsenoside Rg1, ginsenoside Rb1, Astragaloside IV.
According to method of the present invention, wherein carry out differentiating that high performance liquid chromatography A used comprises the steps: to medicinal material pseudo-ginseng and/or the Radix Astragali or their index components
(1) get brave coltfoal hepatitis B preparation appropriate, porphyrize, gets 2g, adds methyl alcohol 40ml, ultrasonic process (such as, power 400 ~ 600W, frequency 35 ~ 45kHz, such as, power 500W, frequency 40kHz) (such as 40 minutes) were (as well known to those skilled in the art 30 ~ 50 minutes, ultrasonic process makes the index components in preparation be dissolved in solvent, therefore the intensity of its ultrasonic process does not also need considered critical), let cool, filter, filtrate evaporate to dryness, the residue 30ml that adds water makes dissolving, filter, the normal butyl alcohol jolting that filtrate water is saturated extracts 2 times, each 20ml, merge normal butyl alcohol liquid, wash twice with strong ammonia solution, each 20ml, get normal butyl alcohol liquid water bath method, residue adds methyl alcohol 2ml makes dissolving, as need testing solution,
(2) separately get notoginsenoside R reference substance, ginsenoside Rg1's reference substance, ginsenoside Rb1's reference substance, Astragaloside IV reference substance, add methyl alcohol and make every 1ml respectively containing the mixed solution of 70 μ g, product solution in contrast;
(3) according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " contained method tests, or according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " contained method test, take octadecylsilane chemically bonded silica as filling agent; Be mobile phase A with water, take acetonitrile as Mobile phase B, the regulation according to the form below carries out gradient elution, and flow velocity is 1ml/min, and column temperature is 35 DEG C, and evaporative light-scattering detector detects;
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) precision draws each 15 μ l of above-mentioned two kinds of solution respectively, injection liquid chromatography, and record chromatogram, compares need testing solution chromatogram and reference substance solution chromatogram.
According to method of the present invention, in wherein said high performance liquid chromatography A, relatively need testing solution chromatogram and reference substance solution chromatogram, if present the chromatographic peak identical with corresponding reference substance retention time in test sample chromatogram respectively, medicinal material pseudo-ginseng then in described brave coltfoal hepatitis B preparation and/or the Radix Astragali or their index components discrimination tests qualified, otherwise defective.
According to method of the present invention, it also comprises the step using high performance liquid chromatography B to differentiate the medicinal material giant knotweed in described brave coltfoal hepatitis B preparation, the red sage root, the fruit of Chinese magnoliavine and/or oriental wormwood or their index components further.
According to method of the present invention, the index components of wherein said medicinal material giant knotweed, the red sage root, the fruit of Chinese magnoliavine and/or oriental wormwood is selected from following one or more: polygonin, tanshin polyphenolic acid B, schizandrin, schizandrin A and chlorogenic acid.
According to method of the present invention, wherein carry out differentiating that high performance liquid chromatography B used comprises the steps: to medicinal material giant knotweed, the red sage root, the fruit of Chinese magnoliavine and/or oriental wormwood or their index components
(1) get brave coltfoal hepatitis B preparation appropriate, porphyrize, gets about 2g, accurately weighed, put in tool plug conical flask, precision adds Diluted Alcohol 100ml, close plug, weighedly weighs, and adds hot reflux 1 hour, let cool, more weighedly to weigh, add the weight that Diluted Alcohol supplies less loss, shake up, filter, get subsequent filtrate, obtain need testing solution;
(2) get polygonin reference substance, tanshin polyphenolic acid B reference substance, schizandrin reference substance, schizandrin A reference substance and chlorogenic acid reference substance, add methyl alcohol and make every 1ml respectively containing the mixed solution of 80 μ g, product solution in contrast;
(3) according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " contained method tests, or according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " contained method test, take octadecylsilane chemically bonded silica as filling agent; Take acetonitrile as mobile phase A, with 0.1% phosphoric acid solution for Mobile phase B, the regulation according to the form below carries out gradient elution; Flow velocity is 0.8ml per minute; Mensuration wavelength is 215nm; Column temperature is 30 DEG C;
(4) precision draws each 15 μ l of above-mentioned two kinds of solution respectively, injection liquid chromatography, and record chromatogram, compares need testing solution chromatogram and reference substance solution chromatogram.
According to method of the present invention, in wherein said high performance liquid chromatography B, relatively need testing solution chromatogram and reference substance solution chromatogram, if present the chromatographic peak identical with corresponding reference substance retention time in test sample chromatogram respectively, medicinal material giant knotweed then in described brave coltfoal hepatitis B preparation, the red sage root, the fruit of Chinese magnoliavine and/or oriental wormwood or their index components discrimination tests qualified, otherwise defective.
According to method of the present invention, it also comprises use high performance liquid chromatography C further and carries out assay to described brave coltfoal hepatitis B preparation, and this assay carries out for both the medicinal material giant knotweed used in preparation and the fruit of Chinese magnoliavine.
High performance liquid chromatography C of the present invention comprises the following steps:
(1) measure according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " institute support methods, or measure according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " institute support method;
(2) chromatographic condition and system suitability: take octadecylsilane chemically bonded silica as filling agent; Take acetonitrile as mobile phase A, with 0.1% phosphoric acid solution for 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; Determined wavelength is 215nm; Theoretical cam curve is pressed polygonin and must not calculate lower than 3000;
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: get schizandrin reference substance and polygonin reference substance respectively appropriate, accurately weighed, add methyl alcohol and make the mixing reference substance solution of every 1ml containing schizandrin 15 μ g, polygonin 160 μ g, to obtain final product;
(4) preparation of need testing solution: get brave coltfoal hepatitis B preparation, determine the average weight of every preparation, gets appropriate (if preparation is capsule, referring to the particle that capsule is in-built or powder, also known as content), porphyrize; Get about 2g, accurately weighed, put in tool plug conical flask, precision adds Diluted Alcohol 100ml, close plug, weighedly weighs, and adds hot reflux 1 hour, lets cool, more weighedly weighs, and adds the weight that Diluted Alcohol supplies less loss, shakes up, filter, get subsequent filtrate, to obtain final product;
(5) determination method: accurate absorption reference substance solution and need testing solution each 5 μ l or 10 μ l respectively, injection liquid chromatography, measure, calculate the giant knotweed that comprises in every preparation in the amount of polygonin (C20H22O8), and/or the fruit of Chinese magnoliavine comprised is in the amount of schizandrin (C24H32O7).
Well-known, for assay, need accurately to take test sample, this point is different from when discrimination test.In the step (4) of above-mentioned assay, " determining the average weight of every preparation ", if described preparation is tablet, then can take to be similar to such mode of operation: get 20, accurately weighed, porphyrize, and precision takes about 2g; Or can take to be similar to such mode of operation: get this product 20, after removing dressing, accurately weighed, porphyrize, precision takes about 2g; Or mode is to determine the average weight of every preparation to take other well known to a person skilled in the art, this average weight can be used for final calculating with the accurate about 2g sample taken; For coating tablet, remove dressing and do not remove dressing all passable.In the step (4) of above-mentioned assay, " determining the average weight of every preparation ", if described preparation is capsule, then can take to be similar to such mode of operation: get this product content under content uniformity item, mixing, porphyrize, get about 2g, accurately weighed; Or mode is to determine the average weight of every preparation to take other well known to a person skilled in the art, this average weight can be used for final calculating with the accurate about 2g sample taken.
According to method of the present invention, wherein said brave coltfoal hepatitis B preparation is prepared by a method comprising the following steps and obtains:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filters, and merging filtrate, is concentrated into the thick paste that relative density is 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 pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, be concentrated into the thick paste that relative density is 1.25 ~ 1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.25 ~ 1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is made preparation, such as tablet, capsule, granule etc.
According to method of the present invention, wherein said brave coltfoal hepatitis B preparation is tablet, and its Chinese crude drug amount preparing 1000 tablets used is: giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
According to method of the present invention, wherein said brave coltfoal hepatitis B preparation is tablet, to prepare 1000, it is in preparation process (5), is to be undertaken by comprising following operation: step (4) gained potpourri is added starch, microcrystalline cellulose, calcium sulphate and dolomol auxiliary materials and mixing, and the aqueous solution adding the Hydroxypropyl methylcellulose of 3% is granulated, 60 DEG C of oven dry, be pressed into 1000, optionally carry out film coating, to obtain final product.
According to method of the present invention, wherein said brave coltfoal hepatitis B preparation is capsule, and its Chinese crude drug amount preparing 2500 seed lac wafers used is: giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
According to method of the present invention, wherein said brave coltfoal hepatitis B preparation is capsule, to prepare 2500, it is in preparation process (5), be undertaken by comprising following operation: step (4) gained potpourri is added starch and makes into 500g in right amount, mixing, incapsulates, make 2500, to obtain final product.
Further, second aspect present invention provides a kind of brave coltfoal hepatitis B tablet, in every 1000, it uses the Chinese crude drug of following amount to prepare: giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
Brave coltfoal hepatitis B tablet according to a second aspect of the present invention, comprising starch, microcrystalline cellulose, calcium sulphate and dolomol.
Brave coltfoal hepatitis B tablet according to a second aspect of the present invention, the amount of the starch wherein in every sheet 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, the amount of the microcrystalline cellulose wherein in every sheet 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, the amount of the calcium sulphate wherein in every sheet 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, the amount of the dolomol wherein in every sheet 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 and obtains:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filters, and merging filtrate, is concentrated into the thick paste that relative density is 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 pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, be concentrated into the thick paste that relative density is 1.25 ~ 1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.25 ~ 1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is added starch, microcrystalline cellulose, calcium sulphate and dolomol auxiliary materials and mixing, add 3% Hydroxypropyl methylcellulose aqueous solution to granulate, 60 DEG C of oven dry, be pressed into 1000, optionally carry out film coating (such as this film-coating take hydroxypropyl methylcellulose as base-material), to obtain final product.
The method that the inspection of capsule content uniformity can refer in [content uniformity] in Pharmacopoeia of the People's Republic of China version four in 2015 the 6th page " 0103 capsule " is carried out; The method of getting during tablet in [weight differential] that weight differential inspection can refer in Pharmacopoeia of the People's Republic of China version four in 2015 the 3rd page " 0101 tablet " is carried out.These methods all well known to a person skilled in the art.Arbitrary embodiment of either side of the present invention or to combine with arbitrary embodiment of 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, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
[method for making]:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filtered, and merging filtrate, is concentrated into the thick paste that relative density is 1.30 (50 DEG C); The dregs of a decoction are dried, and pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, and be concentrated into the thick paste that relative density is 1.30 (50 DEG C), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.30 (50 DEG C), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is added starch 90g, microcrystalline cellulose 60g, calcium sulphate 50g and dolomol 12g auxiliary materials and mixing, add 3% Hydroxypropyl methylcellulose aqueous solution to granulate, 60 DEG C of oven dry, be pressed into 1000, (coating weight gain 3%, thin film coating material is commercial hydroxypropyl methylcellulose aqueous dispersion to film coating , to obtain 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, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
[method for making]:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filtered, and merging filtrate, is concentrated into the thick paste that relative density is 1.35 (50 DEG C); The dregs of a decoction are dried, and pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, and be concentrated into the thick paste that relative density is 1.25 (50 DEG C), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.35 (50 DEG C), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is added starch 200g, microcrystalline cellulose 40g, calcium sulphate 60g and dolomol 8g auxiliary materials and mixing, add 3% Hydroxypropyl methylcellulose aqueous solution to granulate, 60 DEG C of oven dry, be pressed into 1000, (coating weight gain 3%, thin film coating material is commercial hydroxypropyl methylcellulose aqueous dispersion to film coating , to obtain 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, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
[method for making]:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filtered, and merging filtrate, is concentrated into the thick paste that relative density is 1.25 (50 DEG C); The dregs of a decoction are dried, and pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, and be concentrated into the thick paste that relative density is 1.35 (50 DEG C), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.25 (50 DEG C), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is added starch 30g, microcrystalline cellulose 70g, calcium sulphate 30g and dolomol 15g auxiliary materials and mixing, add 3% Hydroxypropyl methylcellulose aqueous solution to granulate, 60 DEG C of oven dry, be pressed into 1000, (coating weight gain 3%, thin film coating material is commercial hydroxypropyl methylcellulose aqueous dispersion to film coating , to obtain 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, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
[method for making]:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filtered, and merging filtrate, is concentrated into the thick paste that relative density is 1.25 (50 DEG C); The dregs of a decoction are dried, and pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, and be concentrated into the thick paste that relative density is 1.35 (50 DEG C), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.25 (50 DEG C), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is added starch 100g, microcrystalline cellulose 50g and dolomol 15g to mix, add 3% Hydroxypropyl methylcellulose aqueous solution to granulate, 60 DEG C of oven dry, be pressed into 1000, (coating weight gain 3%, thin film coating material is commercial hydroxypropyl methylcellulose aqueous dispersion to film coating , to obtain final product.
In order to avoid tablet moisture absorption in Long-term Storage process, wrap film clothing is the way be highly profitable, all the more so for Chinese medicinal tablet, and dressing can improve the overall appearance of medicament.Four of above-described embodiment 1-4 batches of tablets are placed March under room temperature relative humidity is lower than the condition of 60%, find that the tablet clothing layer of embodiment 1-3 is unchanged, and embodiment 4 tablet clothing layer has obvious cracking.In the test supplemented, by slightly doing in the formulation and technology of the tablet of embodiment 1-3 to change, namely only do not add calcium sulphate, gained tablet also finds after processing 3 months equally that these tablet clothing layers all have obvious cracking; And if will slightly do in the formulation and technology of the tablet of embodiment 4 to change, namely add calcium sulphate 30mg, gained tablet also finds after processing 3 months equally that these tablet clothing layers are all unchanged.This shows that in prescription, add calcium sulphate is useful.In addition, in the test supplemented, with reference to formula and the method for making of above-described embodiment 1-4, different is only hydroxypropyl methylcellulose aqueous dispersion film-coating being changed into other model, namely with three, obtains 12 kinds of coated tablets; Gained tablet processes equally and also to find these tablet clothing layers after 3 months it is identical with corresponding embodiment 1-4 tablet clothing layer situation of change respectively, such as, when wrapping up 3 kinds of clothing layers with embodiment 1 tablet, gained 3 kinds of tablets clothing layer after process in 3 months is all unchanged, but when wrapping up 3 kinds of clothing layers with embodiment 4 tablet, gained 3 kinds of tablets clothing layer after process in 3 months all has obvious cracking.Therefore, in Tablets, it is useful for adding calcium sulphate, and above-mentioned benefit cannot be expected from calcium sulphate character at all.
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, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
[method for making]:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filtered, and merging filtrate, is concentrated into the thick paste that relative density is 1.30 (50 DEG C); The dregs of a decoction are dried, and pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, and be concentrated into the thick paste that relative density is 1.30 (50 DEG C), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.30 (50 DEG C), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is added starch and make into 500g in right amount, mixing, incapsulates, makes 2500, obtain capsule.
Test example 1:
Use high performance liquid chromatography A to differentiate the medicinal material pseudo-ginseng in brave coltfoal hepatitis B preparation and the Radix Astragali or their index components, the index components of pseudo-ginseng and the Radix Astragali is: notoginsenoside R, ginsenoside Rg1, ginsenoside Rb1, Astragaloside IV.
According to method of the present invention, wherein carry out differentiating that high performance liquid chromatography A used comprises the steps: to medicinal material pseudo-ginseng and/or the Radix Astragali or their index components
(1) get brave coltfoal hepatitis B preparation appropriate, porphyrize, gets 2g, adds methyl alcohol 40ml, ultrasonic process (power 500W, frequency 40kHz) 40 minutes, lets cool, filter, filtrate evaporate to dryness, the residue 30ml that adds water makes dissolving, filter, the normal butyl alcohol jolting that filtrate water is saturated extracts 2 times, each 20ml, merge normal butyl alcohol liquid, wash twice with strong ammonia solution, each 20ml, get normal butyl alcohol liquid water bath method, residue adds methyl alcohol 2ml makes dissolving, as need testing solution;
(2) separately get notoginsenoside R reference substance, ginsenoside Rg1's reference substance, ginsenoside Rb1's reference substance, Astragaloside IV reference substance, add methyl alcohol and make every 1ml respectively containing the mixed solution of 70 μ g, product solution in contrast;
(3) according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " contained method tests, or it is (well-known according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " contained method test, the HPLC method of two pharmacopeia versions is general), take octadecylsilane chemically bonded silica as filling agent; Be mobile phase A with water, take acetonitrile as Mobile phase B, the regulation according to the form below carries out gradient elution, and flow velocity is 1ml/min, and column temperature is 35 DEG C, and evaporative light-scattering detector detects;
Time (min) Mobile phase A (%) Mobile phase B (%)
0～4 90 10
4～5 90→80 10→20
5～14 80 20 8 -->
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) precision draws each 15 μ l of above-mentioned two kinds of solution respectively, injection liquid chromatography, and record chromatogram, compares need testing solution chromatogram and reference substance solution chromatogram.
According to the method for this test example, check each preparation of foregoing embodiments 1-5 gained.Result shows, and the degree of separation in reference substance solution chromatogram between four kinds of index components is all greater than 3, has excellent degree of separation (well-known, degree of separation is greater than 1.5 just normally gratifying); Degree of separation in need testing solution chromatogram between four kinds of index components is all greater than 3, and each peak is not all by the interference at other assorted peak; In need testing solution chromatogram, the retention time of four kinds of index components is coincide to index components corresponding separately in reference substance solution chromatogram.With regard to these results, as a rule, the discrimination test for these samples is qualified.In addition, the present inventor finds, in this test example, within the scope of 15 ~ 25min, maintenance mobile phase A is 77% is necessary, otherwise Ginsenoside Rg1 and Rb1 can not obtain excellent separating effect therebetween, and degree of separation is less than 1.2; Applicant has made great efforts to attempt using the published various HPLC method of prior art, while all can not obtaining be separated excellent with Astragaloside IV, the effect of Ginsenoside Rg1 and Rb1 excellent separation therebetween can also be realized, not only Astragaloside IV disturbs by other assorted peak, and Ginsenoside Rg1 and Rb1 therebetween degree of separation be less than 1.2.
Test example 2:
Use high performance liquid chromatography B to differentiate the medicinal material giant knotweed in described brave coltfoal hepatitis B preparation, the red sage root, the fruit of Chinese magnoliavine and oriental wormwood or their index components, the index components of medicinal material giant knotweed, the red sage root, the fruit of Chinese magnoliavine and oriental wormwood has: polygonin, tanshin polyphenolic acid B, schizandrin, schizandrin A and chlorogenic acid.
According to method of the present invention, wherein carry out differentiating that high performance liquid chromatography B used comprises the steps: to medicinal material giant knotweed, the red sage root, the fruit of Chinese magnoliavine and oriental wormwood or their index components
(1) get brave coltfoal hepatitis B preparation appropriate, porphyrize, gets about 2g, accurately weighed, put in tool plug conical flask, precision adds Diluted Alcohol 100ml, close plug, weighedly weighs, and adds hot reflux 1 hour, let cool, more weighedly to weigh, add the weight that Diluted Alcohol supplies less loss, shake up, filter, get subsequent filtrate, obtain need testing solution;
(2) get polygonin reference substance, tanshin polyphenolic acid B reference substance, schizandrin reference substance, schizandrin A reference substance and chlorogenic acid reference substance, add methyl alcohol and make every 1ml respectively containing the mixed solution of 80 μ g, product solution in contrast;
(3) according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " contained method tests, or according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " contained method test, take octadecylsilane chemically bonded silica as filling agent; Take acetonitrile as mobile phase A, with 0.1% phosphoric acid solution for Mobile phase B, the regulation according to the form below carries out gradient elution; Flow velocity is 0.8ml per minute; Mensuration wavelength is 215nm; Column temperature is 30 DEG C;
(4) precision draws each 15 μ l of above-mentioned two kinds of solution respectively, injection liquid chromatography, and record chromatogram, compares need testing solution chromatogram and reference substance solution chromatogram.
According to the method for this test example, check each preparation of foregoing embodiments 1-5 gained.Result shows, and the degree of separation in reference substance solution chromatogram between five kinds of index components is all greater than 3, has excellent degree of separation; Degree of separation in need testing solution chromatogram between five kinds of index components is all greater than 3, and each peak is not all by the interference at other assorted peak; In need testing solution chromatogram, the retention time of five kinds of index components is coincide to index components corresponding separately in reference substance solution chromatogram.With regard to these results, as a rule, the discrimination test for these samples is qualified.
In addition, the present inventor finds, in this test example, fine change gradient elution program, all tanshin polyphenolic acid B and chlorogenic acid cannot be separated, such as, change the mobile phase A during 15-28min in upper table into 25%, just tanshin polyphenolic acid B and chlorogenic acid degree of separation cannot be reached more than 1.5; Applicant has made great efforts to attempt using prior art published various HPLC method, all can not obtain the excellent degree of separation being greater than 1.5 between tanshin polyphenolic acid B and chlorogenic acid, say nothing of the effect realizing being greater than 3 degree of separation.
Test example 3:
Use high performance liquid chromatography C to carry out assay to described brave coltfoal hepatitis B preparation, this assay carries out for both the medicinal material giant knotweed used in preparation and the fruit of Chinese magnoliavine.
High performance liquid chromatography C comprises the following steps:
(1) measure according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " institute support methods, or measure according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " institute support method;
(2) chromatographic condition and system suitability: take octadecylsilane chemically bonded silica as filling agent; Take acetonitrile as mobile phase A, with 0.1% phosphoric acid solution for 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; Determined wavelength is 215nm; Theoretical cam curve is pressed polygonin and must not calculate lower than 3000;
(3) preparation of reference substance solution: get schizandrin reference substance and polygonin reference substance respectively appropriate, accurately weighed, add methyl alcohol and make the mixing reference substance solution of every 1ml containing schizandrin 15 μ g, polygonin 160 μ g, to obtain final product;
(4) preparation of need testing solution: get brave coltfoal hepatitis B preparation, determine the average weight of every preparation, gets appropriate (if preparation is capsule, referring to the particle that capsule is in-built or powder, also known as content), porphyrize; Get about 2g, accurately weighed, put in tool plug conical flask, precision adds Diluted Alcohol 100ml, close plug, weighedly weighs, and adds hot reflux 1 hour, lets cool, more weighedly weighs, and adds the weight that Diluted Alcohol supplies less loss, shakes up, filter, get subsequent filtrate, to obtain final product;
(5) determination method: accurate absorption reference substance solution and need testing solution each 5 μ l or 10 μ l respectively, injection liquid chromatography, measure, calculate the giant knotweed that comprises in every preparation in the amount of polygonin (C20H22O8), and/or the fruit of Chinese magnoliavine comprised is in the amount of schizandrin (C24H32O7).
In the gradient elution of above-mentioned high performance liquid chromatography C, schizandrin and polygonin all can realize with other peak the separating effect that degree of separation is greater than 3; But, have been found that trickle change elution program (such as changing mobile phase A during 20 ~ 30min 73% into 75%), schizandrin and the impurity peaks situation of too busy to get away (degree of separation is less than 1.2) of dividing will be caused to occur.Use other chromatographic condition instead, it is such as filling agent with octadecylsilane chemically bonded silica, with methanol-acetonitrile-water (30:10:60) for mobile phase, flow velocity 0.5ml/min, determined wavelength is 303nm, number of theoretical plate by polygonin peak calculate should be not less than 2000 such chromatographic condition time, the separating effect that schizandrin and polygonin all can be greater than 1.5 with other peak degree of separation cannot be obtained; It is such as again filling agent with octadecylsilane chemically bonded silica, with acetonitrile-water (23:77) for mobile phase, flow velocity 0.8ml/min, determined wavelength is 306nm, number of theoretical plate by polygonin peak calculate should be not less than 3000 such chromatographic condition time, the separating effect that schizandrin and polygonin all can be greater than 1.5 with other peak degree of separation cannot be obtained.
In the step (4) of above-mentioned assay, " determining the average weight of every preparation ", if described preparation is tablet, then takes such mode of operation: get 20, accurately weighed, and porphyrize, precision takes about 2g.Determine the average weight of every preparation in this way, this average weight can be used for the accurate about 2g sample taken the content finally calculating polygonin and/or schizandrin in every preparation.For coating tablet, remove dressing and do not remove dressing all passable, there is no materially affect, in this test, need not dressing be removed.In the step (4) of above-mentioned assay, " determine the average weight of every preparation ", if described preparation is capsule, then take such mode of operation: carry out content uniformity mensuration in advance, then this product content under content uniformity item is got, mixing, porphyrize, get about 2g, accurately weighed; Determine the average weight of every preparation like this, this average weight can be used for the accurate about 2g sample taken the content finally calculating polygonin and/or schizandrin in every preparation.
According to the method for this test example, measure each preparation of foregoing embodiments 1-5 gained.Result shows, in each tablet of embodiment 1-4, every tablet containing giant knotweed in polygonin (C20H22O8) all within the scope of 5.3 ~ 7.1mg, be all greater than 4.5mg/ grain; Every tablet containing the fruit of Chinese magnoliavine in schizandrin (C24H32O7) all within the scope of 0.41 ~ 0.83mg, be all greater than 0.32mg/ grain.In the capsule of embodiment 5, every seed lac wafer counts 2.3mg containing giant knotweed with polygonin (C20H22O8), is greater than 1.4mg/ grain; Every seed lac wafer counts 0.22mg containing the fruit of Chinese magnoliavine with schizandrin (C24H32O7), is greater than 0.13mg/ grain.

Claims (10)

1. the method for a brave coltfoal hepatitis B quality of the pharmaceutical preparations control, described brave coltfoal hepatitis B preparation is made up of following 11 taste Chinese medicines and optional pharmaceutic adjuvant: giant knotweed, ant, radix bupleuri, oriental wormwood, Radix Isatidis, the fruit of Chinese wolfberry, the Radix Astragali, pseudo-ginseng, the red sage root, the fruit of Chinese magnoliavine, date, and the method comprises the step using high performance liquid chromatography A to differentiate the medicinal material pseudo-ginseng in described brave coltfoal hepatitis B preparation and/or the Radix Astragali or their index components.
2. method according to claim 1, wherein:
Described brave coltfoal hepatitis B preparation is tablet, capsule or granule;
The medicinal material ratio preparing described brave coltfoal hepatitis B preparation is: giant knotweed 665 weight portion, ant 287.5 weight portion, radix bupleuri 132.5 weight portion, oriental wormwood 250 weight portion, Radix Isatidis 332.5 weight portion, the fruit of Chinese wolfberry 132.5 weight portion, the Radix Astragali 167.5 weight portion, pseudo-ginseng 17.5 weight portion, the red sage root 167.5 weight portion, the fruit of Chinese magnoliavine 132.5 weight portion, date 50 weight portion; And/or
The index components of described pseudo-ginseng and/or the Radix Astragali is selected from following one or more: notoginsenoside R, ginsenoside Rg1, ginsenoside Rb1, Astragaloside IV.
3. method according to claim 1, wherein carries out differentiating that high performance liquid chromatography A used comprises the steps: to medicinal material pseudo-ginseng and/or the Radix Astragali or their index components
(1) get brave coltfoal hepatitis B preparation appropriate, porphyrize, gets 2g, adds methyl alcohol 40ml, ultrasonic process (such as, power 400 ~ 600W, frequency 35 ~ 45kHz, such as, power 500W, frequency 40kHz) (such as 40 minutes) were (as well known to those skilled in the art 30 ~ 50 minutes, ultrasonic process makes the index components in preparation be dissolved in solvent, therefore the intensity of its ultrasonic process does not also need considered critical), let cool, filter, filtrate evaporate to dryness, the residue 30ml that adds water makes dissolving, filter, the normal butyl alcohol jolting that filtrate water is saturated extracts 2 times, each 20ml, merge normal butyl alcohol liquid, wash twice with strong ammonia solution, each 20ml, get normal butyl alcohol liquid water bath method, residue adds methyl alcohol 2ml makes dissolving, as need testing solution,
(2) separately get notoginsenoside R reference substance, ginsenoside Rg1's reference substance, ginsenoside Rb1's reference substance, Astragaloside IV reference substance, add methyl alcohol and make every 1ml respectively containing the mixed solution of 70 μ g, product solution in contrast;
(3) according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " contained method tests, or according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " contained method test, take octadecylsilane chemically bonded silica as filling agent; Be mobile phase A with water, take acetonitrile as Mobile phase B, the regulation according to the form below carries out gradient elution, and flow velocity is 1ml/min, and column temperature is 35 DEG C, and evaporative light-scattering detector detects;
(4) precision draws each 15 μ l of above-mentioned two kinds of solution respectively, injection liquid chromatography, and record chromatogram, compares need testing solution chromatogram and reference substance solution chromatogram;
Optionally further, in wherein said high performance liquid chromatography A, relatively need testing solution chromatogram and reference substance solution chromatogram, if present the chromatographic peak identical with corresponding reference substance retention time in test sample chromatogram respectively, medicinal material pseudo-ginseng then in described brave coltfoal hepatitis B preparation and/or the Radix Astragali or their index components discrimination tests qualified, otherwise defective.
4. method according to claim 1, it also comprises the step using high performance liquid chromatography B to differentiate the medicinal material giant knotweed in described brave coltfoal hepatitis B preparation, the red sage root, the fruit of Chinese magnoliavine and/or oriental wormwood or their index components further; Optional further, the index components of wherein said medicinal material giant knotweed, the red sage root, the fruit of Chinese magnoliavine and/or oriental wormwood is selected from following one or more: polygonin, tanshin polyphenolic acid B, schizandrin, schizandrin A and chlorogenic acid.
5. method according to claim 4, wherein carries out differentiating that high performance liquid chromatography B used comprises the steps: to medicinal material giant knotweed, the red sage root, the fruit of Chinese magnoliavine and/or oriental wormwood or their index components
(1) get brave coltfoal hepatitis B preparation appropriate, porphyrize, gets about 2g, accurately weighed, put in tool plug conical flask, precision adds Diluted Alcohol 100ml, close plug, weighedly weighs, and adds hot reflux 1 hour, let cool, more weighedly to weigh, add the weight that Diluted Alcohol supplies less loss, shake up, filter, get subsequent filtrate, obtain need testing solution;
(2) get polygonin reference substance, tanshin polyphenolic acid B reference substance, schizandrin reference substance, schizandrin A reference substance and chlorogenic acid reference substance, add methyl alcohol and make every 1ml respectively containing the mixed solution of 80 μ g, product solution in contrast;
(3) according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " contained method tests, or according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " contained method test, take octadecylsilane chemically bonded silica as filling agent; Take acetonitrile as mobile phase A, with 0.1% phosphoric acid solution for Mobile phase B, the regulation according to the form below carries out gradient elution; Flow velocity is 0.8ml per minute; Mensuration wavelength is 215nm; Column temperature is 30 DEG C;
(4) precision draws each 15 μ l of above-mentioned two kinds of solution respectively, injection liquid chromatography, and record chromatogram, compares need testing solution chromatogram and reference substance solution chromatogram;
Optionally further, in wherein said high performance liquid chromatography B, relatively need testing solution chromatogram and reference substance solution chromatogram, if present the chromatographic peak identical with corresponding reference substance retention time in test sample chromatogram respectively, medicinal material giant knotweed then in described brave coltfoal hepatitis B preparation, the red sage root, the fruit of Chinese magnoliavine and/or oriental wormwood or their index components discrimination tests qualified, otherwise defective.
6., according to the method for claim 1-5, it also comprises use high performance liquid chromatography C further and carries out assay to described brave coltfoal hepatitis B preparation, and this assay carries out for both the medicinal material giant knotweed used in preparation and the fruit of Chinese magnoliavine; Optionally further, described high performance liquid chromatography C comprises the following steps:
(1) measure according to Pharmacopoeia of the People's Republic of China version in 2010 annex 36 pages of " annex VI D high performance liquid chromatography " institute support methods, or measure according to Pharmacopoeia of the People's Republic of China version in 2015 four the 59th page " 0512 high performance liquid chromatography " institute support method;
(2) chromatographic condition and system suitability: take octadecylsilane chemically bonded silica as filling agent; Take acetonitrile as mobile phase A, with 0.1% phosphoric acid solution for 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; Determined wavelength is 215nm; Theoretical cam curve is pressed polygonin and must not calculate lower than 3000;
(3) preparation of reference substance solution: get schizandrin reference substance and polygonin reference substance respectively appropriate, accurately weighed, add methyl alcohol and make the mixing reference substance solution of every 1ml containing schizandrin 15 μ g, polygonin 160 μ g, to obtain final product;
(4) preparation of need testing solution: get brave coltfoal hepatitis B preparation, determine the average weight of every preparation, gets appropriate (if preparation is capsule, referring to the particle that capsule is in-built or powder, also known as content), porphyrize; Get about 2g, accurately weighed, put in tool plug conical flask, precision adds Diluted Alcohol 100ml, close plug, weighedly weighs, and adds hot reflux 1 hour, lets cool, more weighedly weighs, and adds the weight that Diluted Alcohol supplies less loss, shakes up, filter, get subsequent filtrate, to obtain final product;
(5) determination method: accurate absorption reference substance solution and need testing solution each 5 μ l or 10 μ l respectively, injection liquid chromatography, measure, calculate the giant knotweed that comprises in every preparation in the amount of polygonin (C20H22O8), and/or the fruit of Chinese magnoliavine comprised is in the amount of schizandrin (C24H32O7).
7., according to the method for claim 1-6, wherein said brave coltfoal hepatitis B preparation is prepared by a method comprising the following steps and obtains:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filters, and merging filtrate, is concentrated into the thick paste that relative density is 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 pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, be concentrated into the thick paste that relative density is 1.25 ~ 1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.25 ~ 1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is made preparation, such as tablet, capsule, granule etc.
8. according to the method for claim 1-7, wherein:
Described brave coltfoal hepatitis B preparation is tablet, and its Chinese crude drug amount preparing 1000 tablets used is: giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g;
Described brave coltfoal hepatitis B preparation is tablet, to prepare 1000, it is in preparation process (5), undertaken by comprising following operation: step (4) gained potpourri is added starch, microcrystalline cellulose, calcium sulphate and dolomol auxiliary materials and mixing, the aqueous solution adding the Hydroxypropyl methylcellulose of 3% is granulated, and 60 DEG C of oven dry, are pressed into 1000, optionally carry out film coating, to obtain final product;
Described brave coltfoal hepatitis B preparation is capsule, and its Chinese crude drug amount preparing 2500 seed lac wafers used is: giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g; And/or
Described brave coltfoal hepatitis B preparation is capsule, and to prepare 2500, it is in preparation process (5), be undertaken by comprising following operation: step (4) gained potpourri is added starch and makes into 500g in right amount, mixing, incapsulates, make 2500, to obtain final product.
9. a brave coltfoal hepatitis B tablet, in every 1000, it uses the Chinese crude drug of following amount to prepare: giant knotweed 665g, ant 287.5g, radix bupleuri 132.5g, oriental wormwood 250g, Radix Isatidis 332.5g, fruit of Chinese wolfberry 132.5g, Radix Astragali 167.5g, pseudo-ginseng 17.5g, red sage root 167.5g, fruit of Chinese magnoliavine 132.5g, date 50g.
10. brave coltfoal hepatitis B tablet according to claim 9, is characterized in that following any one or multinomial:
Comprising starch, microcrystalline cellulose, calcium sulphate and dolomol;
The amount of the starch wherein in every sheet is 30 ~ 300mg, such as 30 ~ 250mg, such as 30 ~ 200mg;
The amount of the microcrystalline cellulose wherein in every sheet is 20 ~ 100mg, such as 30 ~ 80mg, such as 40 ~ 70mg;
The amount of the calcium sulphate wherein in every sheet is 20 ~ 100mg, such as 30 ~ 80mg, such as 30 ~ 60mg;
The amount of the dolomol wherein in every sheet is 5 ~ 20mg, such as 5 ~ 15mg, such as 8 ~ 15mg; And/or
It is prepared by a method comprising the following steps and obtains:
(1) with 11 taste medicinal materials, Radix Notoginseng powder is broken into fine powder;
(2) ant removing impurity, cleaning, boiling twice, each 1 hour, decocting liquid filters, and merging filtrate, is concentrated into the thick paste that relative density is 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 pulverize, for subsequent use;
(3) Radix Astragali, the fruit of Chinese wolfberry, date boiling secondary, each 1 hour, decocting liquid filtered, merging filtrate, be concentrated into the thick paste that relative density is 1.25 ~ 1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)), the dregs of a decoction are for subsequent use;
(4) get the three taste dregs of a decoction such as giant knotweed, Radix Isatidis, oriental wormwood, the red sage root, the fruit of Chinese magnoliavine, radix bupleuri and the above-mentioned Radix Astragali, adding 70% alcohol reflux extracts three times, 1.5 hours first times, second and third time each 1 hour, merge extract, filter, reclaim ethanol, be concentrated into the thick paste that relative density is 1.25 ~ 1.35 (50 DEG C) (such as relative density is 1.30 (50 DEG C)), merge with above-mentioned thick paste, mix with ant powder, Radix Notoginseng powder, dry, pulverize, sieve;
(5) step (4) gained potpourri is added starch, microcrystalline cellulose, calcium sulphate and dolomol auxiliary materials and mixing, add 3% Hydroxypropyl methylcellulose aqueous solution to granulate, 60 DEG C of oven dry, be pressed into 1000, optionally carry out film coating (such as this film-coating take hydroxypropyl methylcellulose as base-material), to obtain final product.
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