CN101254284A - Rheumatism treating medicine combination, preparation and quality control method - Google Patents

Rheumatism treating medicine combination, preparation and quality control method Download PDF

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CN101254284A
CN101254284A CNA2007100640648A CN200710064064A CN101254284A CN 101254284 A CN101254284 A CN 101254284A CN A2007100640648 A CNA2007100640648 A CN A2007100640648A CN 200710064064 A CN200710064064 A CN 200710064064A CN 101254284 A CN101254284 A CN 101254284A
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radix
weight portion
filtrate
adds
solution
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CN101254284B (en
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付立家
付建家
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Beijing Asia East Bio Pharmaceutical Co Ltd
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Beijing Asia East Bio Pharmaceutical Co Ltd
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Abstract

The invention discloses a pharmaceutical composition for the treatment of rheumatism, a preparation method and a quality control method. The pharmaceutical raw materials of the pharmaceutical composition of the invention is composed of prepared common monkshood mother root, prepared kusnezoff monkshood root, largeleaf gentian root, dahurian angelica root, liquoric root, sevenlobed yam rhizome, Ningpo yam rhizome, coix seed, pedate pinallia jackinthepulpit rhizome (roasted), safflower, white paeony root and slenderstyle acanthopanax bark. The preparation method is that: the dahurian angelica root, the coix seed and the Chinese angelica are smashed into first fine powder; the water is added in the prepared common monkshood mother root, the prepared kusnezoff monkshood root and the largeleaf gentian root for boiling, the decoction solution is merged and filtered to obtain the first filtrate for standby; paniculate swallowwort root is distilled by adding water, the distilled liquid is refrigerated till the precipitation of white crystals, the filtration is carried out to obtain the second filtrate, the crystals are dried naturally for standby, the second filtrate, the medicine residues and other fine medicines are boiled by adding water, the decoction solution is merged and filtered for obtain the third filtrate, the third filtrate and the first filtrate are merged and condensed into a thick paste; the first fine powder is added in the thick paste for even mixing, drying and smashing, so as to obtain the second fine powder, the white crystals are added for preparing a preparation. The pharmaceutical composition of the invention has very good efficacy for the treatment of the rheumatism.

Description

The rheumatismal pharmaceutical composition of a kind of treatment and preparation method and method of quality control
Invention field
The present invention relates to a kind of pharmaceutical composition and preparation method and method of quality control, the rheumatismal pharmaceutical composition of particularly a kind of treatment and preparation method and method of quality control.
Background technology
Rheumatism is the abbreviation of rheumatism, and general reference influences BJM and surrounding soft tissue thereof, as a big group disease such as synovial bursa, tendon, fascia, blood vessel, nerve.Rheumatism comprises diffusivity connective tissue disease (as rheumatoid arthritis, systemic lupus erythematosus (sle), dry syndrome, inflammatory myopathy, scleroderma, mixed connective tissue disease, Behcet disease etc.), systemic vasculitis, SpA (as ankylosing spondylitis, reactive arthritis, auspicious special syndrome etc.), osteoarthritis, osteoporosis etc., and hundreds of is above to involve the disease general name of connective tissues such as bone, joint.
Various rheumatism are the autoimmunity rheumatism particularly, and whole body multisystem and multiple organ injury are often arranged, and has complicated symptom, often becomes difficult miscellaneous diseases because of clinical manifestation complicated and changeable.The rheumatismal course of disease is chronic a bit, protracted course of disease, and some breaks out onset, and its diagnosis and treatment are quite loaded down with trivial details and complicated.If the treatment that rheumatism can not get holding water, the joint, muscle, pathological changes such as skeleton can cause dysfunction and deformity, stay lifelong deformity, even threat to life, and consequence is extremely serious.
The western medical treatment rheumatism is mainly used medicines such as non-steroidal anti-inflammatory drug, immunosuppressant and hormone at present, though pain relieving temporarily, relief of symptoms, play certain therapeutical effect, yet but can not fundamentally treat rheumatism, and long-term prescription also may destroy the human immune system, internal organs major injuries such as irreversible stomach, liver, kidney finally occur, and the side effect of its generation definitely can not be ignored.
Motherland's medical science has rich experience to the treatment of " rheumatism " for a long time, many effective proved recipes have been accumulated, compare doctor trained in Western medicine, motherland's medical science determined curative effect, easy to use, that untoward reaction is little etc. is with the obvious advantage, therefore preferablyly apply clinically.
Summary of the invention
The object of the invention is to provide a kind of pharmaceutical composition; Another purpose of the present invention is to provide a kind of treatment rheumatismal pharmaceutical composition; The 3rd purpose of the present invention is to provide this preparation of drug combination method; The 4th purpose of the present invention is to provide the method for quality control of this pharmaceutical composition.
The present invention seeks to be achieved through the following technical solutions:
The crude drug of pharmaceutical composition of the present invention consists of: Radix Aconiti Preparata 30-80 weight portion, Radix Aconiti Kusnezoffii Preparata 30-80 weight portion, Radix Gentianae Macrophyllae 30-80 weight portion, Radix Angelicae Dahuricae 30-80 weight portion, Radix Glycyrrhizae 30-80 weight portion, Rhizoma Dioscoreae Hypoglaucae 70-130 weight portion, Rhizoma Dioscoreae Nipponicae 70-130 weight portion, Semen Coicis 70-130 weight portion, Rhizoma Arisaematis (processing) 30-80 weight portion, Flos Carthami 70-130 weight portion, Radix Paeoniae Alba 30-80 weight portion, Cortex Acanthopancis 120-200 weight portion.
The crude drug of pharmaceutical composition of the present invention is formed can also be Radix Aconiti Preparata 30-80 weight portion, Radix Aconiti Kusnezoffii Preparata 30-80 weight portion, Radix Gentianae Macrophyllae 30-80 weight portion, Radix Angelicae Dahuricae 30-80 weight portion, Radix Glycyrrhizae 30-80 weight portion, Rhizoma Dioscoreae Hypoglaucae 70-130 weight portion, Rhizoma Dioscoreae Nipponicae 70-130 weight portion, Semen Coicis 70-130 weight portion, Rhizoma Arisaematis (processing) 30-80 weight portion, Flos Carthami 70-130 weight portion, Radix Angelicae Sinensis 30-80 weight portion, Radix Cynanchi Paniculati 120-200 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 30-50 weight portion, Radix Aconiti Kusnezoffii Preparata 60-80 weight portion, Radix Gentianae Macrophyllae 30-50 weight portion, Radix Angelicae Dahuricae 60-80 weight portion, Radix Glycyrrhizae 30-50 weight portion, Rhizoma Dioscoreae Hypoglaucae 110-130 weight portion, Rhizoma Dioscoreae Nipponicae 70-90 weight portion, Semen Coicis 110-130 weight portion, Rhizoma Arisaematis (processing) 30-50 weight portion, Flos Carthami 110-130 weight portion, Radix Angelicae Sinensis 30-50 weight portion, Radix Cynanchi Paniculati 170-200 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 40.25 weight portions, Radix Aconiti Kusnezoffii Preparata 70.25 weight portions, Radix Gentianae Macrophyllae 40.25 weight portions, the Radix Angelicae Dahuricae 70.25 weight portions, Radix Glycyrrhizae 40.25 weight portions, Rhizoma Dioscoreae Hypoglaucae 120.5 weight portions, Rhizoma Dioscoreae Nipponicae 80.5 weight portions, Semen Coicis 120.5 weight portions, Rhizoma Arisaematis (processing) 40.25 weight portions, Flos Carthami 120.5 weight portions, Radix Angelicae Sinensis 40.25 weight portions, Radix Cynanchi Paniculati 185.75 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 45.25 weight portions, Radix Aconiti Kusnezoffii Preparata 65.25 weight portions, Radix Gentianae Macrophyllae 45.25 weight portions, the Radix Angelicae Dahuricae 65.25 weight portions, Radix Glycyrrhizae 45.25 weight portions, Rhizoma Dioscoreae Hypoglaucae 115.5 weight portions, Rhizoma Dioscoreae Nipponicae 85.5 weight portions, Semen Coicis 115.5 weight portions, Rhizoma Arisaematis (processing) 45.25 weight portions, Flos Carthami 115.5 weight portions, Radix Angelicae Sinensis 45.25 weight portions, Radix Cynanchi Paniculati 175.75 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 60-80 weight portion, Radix Aconiti Kusnezoffii Preparata 30-50 weight portion, Radix Gentianae Macrophyllae 60-80 weight portion, Radix Angelicae Dahuricae 30-50 weight portion, Radix Glycyrrhizae 60-80 weight portion, Rhizoma Dioscoreae Hypoglaucae 70-90 weight portion, Rhizoma Dioscoreae Nipponicae 110-130 weight portion, Semen Coicis 70-90 weight portion, Rhizoma Arisaematis (processing) 60-80 weight portion, Flos Carthami 70-90 weight portion, Radix Angelicae Sinensis 60-80 weight portion, Radix Cynanchi Paniculati 120-150 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 70.25 weight portions, Radix Aconiti Kusnezoffii Preparata 40.25 weight portions, Radix Gentianae Macrophyllae 70.25 weight portions, the Radix Angelicae Dahuricae 40.25 weight portions, Radix Glycyrrhizae 70.25 weight portions, Rhizoma Dioscoreae Hypoglaucae 80.5 weight portions, Rhizoma Dioscoreae Nipponicae 120.5 weight portions, Semen Coicis 80.5 weight portions, Rhizoma Arisaematis (processing) 70.25 weight portions, Flos Carthami 80.5 weight portions, Radix Angelicae Sinensis 70.25 weight portions, Radix Cynanchi Paniculati 125.75 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 65.25 weight portions, Radix Aconiti Kusnezoffii Preparata 45.25 weight portions, Radix Gentianae Macrophyllae 65.25 weight portions, the Radix Angelicae Dahuricae 45.250 weight portions, Radix Glycyrrhizae 65.25 weight portions, Rhizoma Dioscoreae Hypoglaucae 85.5 weight portions, Rhizoma Dioscoreae Nipponicae 115.25 weight portions, Semen Coicis 85.5 weight portions, Rhizoma Arisaematis (processing) 65.25 weight portions, Flos Carthami 85.5 weight portions, Radix Angelicae Sinensis 65.25 weight portions, Radix Cynanchi Paniculati 145.75 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 30-40 weight portion, Radix Aconiti Kusnezoffii Preparata 30-40 weight portion, Radix Gentianae Macrophyllae 70-80 weight portion, Radix Angelicae Dahuricae 70-80 weight portion, Radix Glycyrrhizae 30-40 weight portion, Rhizoma Dioscoreae Hypoglaucae 70-80 weight portion, Rhizoma Dioscoreae Nipponicae 120-130 weight portion, Semen Coicis 120-130 weight portion, Rhizoma Arisaematis (processing) 30-40 weight portion, Flos Carthami 70-80 weight portion, Radix Angelicae Sinensis 70-80 weight portion, Radix Cynanchi Paniculati 180-200 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 35.25 weight portions, Radix Aconiti Kusnezoffii Preparata 35.25 weight portions, Radix Gentianae Macrophyllae 75.25 weight portions, the Radix Angelicae Dahuricae 75.25 weight portions, Radix Glycyrrhizae 35.25 weight portions, Rhizoma Dioscoreae Hypoglaucae 75.5 weight portions, Rhizoma Dioscoreae Nipponicae 125.5 weight portions, Semen Coicis 125.5 weight portions, Rhizoma Arisaematis (processing) 35.25 weight portions, Flos Carthami 75.5 weight portions, Radix Angelicae Sinensis 75.25 weight portions, Radix Cynanchi Paniculati 190.75 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 51-59 weight portion, Radix Aconiti Kusnezoffii Preparata 51-59 weight portion, Radix Gentianae Macrophyllae 51-59 weight portion, Radix Angelicae Dahuricae 51-59 weight portion, Radix Glycyrrhizae 51-59 weight portion, Rhizoma Dioscoreae Hypoglaucae 100-109 weight portion, Rhizoma Dioscoreae Nipponicae 100-109 weight portion, Semen Coicis 100-109 weight portion, Rhizoma Arisaematis (processing) 51-59 weight portion, Flos Carthami 100-109 weight portion, Radix Angelicae Sinensis 51-59 weight portion, Radix Cynanchi Paniculati 155-165 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Radix Aconiti Preparata 53.25 weight portions, Radix Aconiti Kusnezoffii Preparata 53.25 weight portions, Radix Gentianae Macrophyllae 53.25 weight portions, the Radix Angelicae Dahuricae 53.25 weight portions, Radix Glycyrrhizae 53.25 weight portions, Rhizoma Dioscoreae Hypoglaucae 106.5 weight portions, Rhizoma Dioscoreae Nipponicae 106.5 weight portions, Semen Coicis 106.5 weight portions, Rhizoma Arisaematis (processing) 53.25 weight portions, Flos Carthami 106.5 weight portions, Radix Angelicae Sinensis 53.25 weight portions, Radix Cynanchi Paniculati 159.75 weight portions.
Preparation of pharmaceutical compositions method of the present invention is: above 12 flavors, and the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 6-10 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 1-3 time, and each 1-3 hour, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 3-6 times of parts by volume, and distillate cold preservation under 2-10 ℃ of condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 6-10 times of parts by volume boils 1-3 time, each 1-3 hour, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.20～1.40 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the preparation of clinical acceptance.
Preparation of pharmaceutical compositions method of the present invention is preferably: above 12 flavors, and the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 8 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 2 times, and each 2 hours, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 5 times of parts by volume, and distillate cold preservation under 2-10 ℃ of condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 8 times of parts by volume boils 2 times, each 2 hours, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.30 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the oral solid formulation of clinical acceptance.
Pharmaceutical composition method of quality control of the present invention comprises one or more in following discrimination method and/or the assay:
Assay: the test of chromatographic condition and system suitability: with octadecylsilane chemically bonded silica is filler: with 50-80: 20-50: 1-5: the methanol-water-chloroform of 0-0.5 ratio-triethylamine is a mobile phase; Detect wavelength 240nm, number of theoretical plate calculates by the aconitine peak and is not less than 1500;
The preparation of reference substance solution: it is an amount of that the aconitine reference substance decided in accurate title, adds methylene chloride and make the solution of 50-100 μ g/ml;
The preparation of need testing solution: precision takes by weighing the preparation content that is equivalent to crude drug content 1/120, and it is an amount of to add kieselguhr, and mixing adds ether 50ml, ammonia solution 2ml, and reflux, extract, 1 hour is put cold filtration, and with ether washing nozzle and residue, washing liquid is incorporated filtrate into; Filtrate is put and is added 15ml washing twice in the separatory funnel, merges water liquid, and the 20ml that adds diethyl ether washing discards water layer, merges ether, volatilizes ether,, adds methylene chloride to scale to the 5ml volumetric flask with the dichloromethane solution transfer, shakes up, promptly;
Assay method: above solution filters with 0.45 μ m microporous filter membrane, gets subsequent filtrate, and accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn measured promptly;
Pharmaceutical composition per unit preparation of the present invention contains Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata with aconitine C 34H 47NO 11Meter must not be less than 0.02mg;
Discrimination method: A, get the preparation content that is equivalent to crude drug content 1/60, the 50ml that adds diethyl ether, jolting was left standstill 30 minutes, filtered the filtrate evaporate to dryness; Residue adds ethyl acetate 1ml dissolving; Other gets imperatorin, isoimperatorin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 4 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 2-4: the petroleum ether of 1-3 ratio (30～60 ℃)-ether is developing solvent, is launching below 25 ℃, takes out, and dries, and puts under the 365nm uviol lamp and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get the preparation content that is equivalent to crude drug content 1/50, the 30ml that adds diethyl ether, heating and refluxing extraction 30 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 1g, the 10ml that adds diethyl ether, and supersound process 10 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution; Put respectively on same silica gel g thin-layer plate, with 7.5-11.5: the petroleum ether of 0.3-0.7 ratio (60～90 ℃)-ethyl acetate is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
Pharmaceutical composition method of quality control of the present invention is preferably as follows one or more in discrimination method and/or the assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica was filler: with 65: 35: 3: the methanol-water-chloroform of 0.2 ratio-triethylamine is a mobile phase; Detect wavelength 240nm, number of theoretical plate calculates by the aconitine peak and is not less than 1500;
The preparation of reference substance solution: it is an amount of that the aconitine reference substance decided in accurate title, adds methylene chloride and make the solution of 80 μ g/ml;
The preparation of need testing solution: precision takes by weighing gets the preparation content that is equivalent to crude drug content 1/120, and it is an amount of to add kieselguhr, and mixing adds ether 50ml, ammonia solution 2ml, and reflux, extract, 1 hour is put cold filtration, and with ether washing nozzle and residue, washing liquid is incorporated filtrate into; Filtrate is put and is added 15ml washing twice in the separatory funnel, merges water liquid, and the 20ml that adds diethyl ether washing discards water layer, merges ether, volatilizes ether,, adds methylene chloride to scale to the 5ml volumetric flask with the dichloromethane solution transfer, shakes up, promptly;
Assay method: above solution filters with 0.45 μ m microporous filter membrane, gets subsequent filtrate, and accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn measured promptly;
Pharmaceutical composition per unit preparation of the present invention contains Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata in aconitine C34H47NO11, must not be less than 0.02mg;
Discrimination method: A, get the preparation content that is equivalent to crude drug content 1/60, the 50ml that adds diethyl ether, jolting was left standstill 30 minutes, filtered the filtrate evaporate to dryness; Residue adds ethyl acetate 1ml dissolving; Other gets imperatorin, isoimperatorin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 4 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with petroleum ether (30～60 ℃)-ether of 3: 2 ratios, launching below 25 ℃, take out, dry, put under the 365nm uviol lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get the preparation content that is equivalent to crude drug content 1/50, the 30ml that adds diethyl ether, heating and refluxing extraction 30 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 1g, the 10ml that adds diethyl ether, and supersound process 10 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution; Putting respectively on same silica gel g thin-layer plate, is developing solvent with petroleum ether (60～90 ℃)-ethyl acetate of 9.5: 0.5 ratios, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
Pharmaceutical composition dispeiling pathogenic wind and removing dampness of the present invention, promoting blood circulation to remove obstruction in the collateral, reducing swelling and alleviating pain, kidney-supplementing liver-boosting, bone strengthening are kept fit, and can fundamentally treat rheumatism, such as chronic arthritis, gouty arthritis, sciatica, lumbar intervertebral disc (taking off) is outstanding, loose spondylitis, spinal canal stenosis, calcanean spur, Kaschin-Beck disease and senile lumbago and skelalgia, diseases such as soft tissue injury and other kinds pain.Especially suitable treatment hyperosteogeny, rheumatic arthritis or rheumatalgia.Pharmaceutical composition of the present invention confirms through experimentation: active ingredient can be passed through nervous system indirect stimulation hypophysis cerebri, makes hypercorticalismus, and the 17-hydroxy-11-dehydrocorticosterone secretion increases, and antihistaminic is secreted with pain relieving; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae are to rheumatism in the side, and rheumatoid factor has stronger affinity, can the direct killing virulence factor, and expelling wind and removing dampness, wet meridian and relieving pain, detumescence and apocenosis; Suppress the synovium of joint cell proliferation, the blocking condition sustainable development; Improve microcirculation in human body, inflammation-inhibiting reaction, ease the pain; Strengthen the immune function of bone marrow rapidly, the healthy blood circulation of activated bone marrow is eliminated rheumatism, softening bony spur.
The present composition is compared existing preparation bony spur tablet and is possessed good drug effect, and scope of the present invention through screening, finds in some scope of compositions, to possess more outstanding drug effect unexpectedly when can realizing drug effect of the present invention.
The method of quality control of Chinese medicine composition provided by the present invention, be by obtaining behind the creative experiment sieving of big measuring, pass through screening in the discrimination method to sample treatment, the selection of developing solvent, make and differentiate that specificity is fine, and method is economic and practical, the result is quick, and can both use different lamellaes.Pass through screening in the content assaying method to sample, test sample processing method, the selection of developing solvent, make content assaying method effectivelyly to carry out quality control, and compare more stable that product that additive method measures shows on drug effect with the product that this method is measured to product.
Following experimental example and embodiment are used to further specify the present invention but are not limited to the present invention
The thin layer discrimination method test of experimental example 1 Radix Angelicae Dahuricae
1, the ether soak time was preferred during sample solution prepared among the discrimination method A of the present invention:
Get totally 5 parts of pharmaceutical preparation 5g of the present invention, soak different time with ether, jolting constantly filters, and filtrate volatilizes ether, and residue adds ethyl acetate 1ml makes dissolving, measures wherein imperatorin content, the results are shown in following table:
Table 1 ether soak time optimization experiment result
Soak time (min) 10 20 30 40 50
Imperatorin content (mg) 65.3 84.2 97.6 97.7 97.6
As can be seen from Table 1, ether lixiviate 30min just can extract imperatorin wherein fully, is 30min so this tests preferred extraction time.
2, developing solvent consumption proportion preferred among the discrimination method A of the present invention:
Get need testing solution 5 μ l, point is on different silica gel g thin-layer plates, using petroleum ether (30-60 ℃)-ether proportioning respectively is that 2: 3,3: 3,4: 3,3: 2,2: 1 developing solvent launches, take out, dry, put under the uviol lamp (365nm) and inspect, observe the unfolded effect of each speckle of test sample on each lamellae, the results are shown in following table:
Table 2 developing solvent consumption proportion optimization experiment result
The developing solvent proportioning 2∶3 3∶3 4∶3 3∶2 2∶1
Launch effect Very poor Difference Relatively poor Good Difference
Developing solvent proportioning as can be seen from Table 2 is 3: 2 o'clock, and it is best that need testing solution launches effect, and appearance hangover, principal spot separate phenomenons such as bad.
3, sample solution point sample amount preferred among the discrimination method A of the present invention:
Get need testing solution 1 μ l, 2 μ l, 3 μ l, 4 μ l, reference substance solution 4 μ l, point is on same silica gel g thin-layer plate, with petroleum ether (30-60 ℃)-ether proportioning is the developing solvent expansion of (3: 2), take out, dry, put under the uviol lamp (365nm) and inspect, observe the effect of test sample principal spot colour developing on the lamellae, the results are shown in following table:
Table 3 sample solution point sample amount optimization experiment result
The point sample amount 1μl 2μl 3μl 4μl
Effect Test sample is at corresponding reference substance position immaculate Test sample is very shallow in corresponding reference substance position spot colors Test sample is shallow in corresponding reference substance position spot colors Test sample is good at corresponding reference substance position speckle color developing effect
Test sample point sample amount is when 4 μ l as can be seen from Table 3, and color developing effect is good on lamellae, is fit to test requirements document.
4, negative control test
Get the negative sample that lacks the Radix Angelicae Dahuricae, prepare negative control solution, launch the back and corresponding speckle on the reference substance solution correspondence position, do not occur, illustrate that selected identification experiment specificity is strong according to need testing solution preparation method among the above-mentioned discrimination method A.
The discrimination method test of experimental example 2 Radix Angelicae Sinensis
1, the 30ml that adds diethyl ether in the sample solution preparation among the discrimination method B of the present invention, reflux and ultrasonic extracting method preferably:
Get totally 5 parts of pharmaceutical preparation 5g of the present invention, the 30ml that adds diethyl ether, reflux and supersound extraction 30min, filter, filtrate volatilizes, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution, put respectively on same silica gel g thin-layer plate, be developing solvent with petroleum ether (60-90 ℃)-ethyl acetate (9.5: 0.5), launch, take out, dry, put under the ultra-violet lamp and inspect, investigate the separation and the colour developing situation of lamellae test sample speckle, the results are shown in following table:
Table 4 sample solution prepares extracting method optimization experiment result
Extracting method Reflux, extract, Supersound extraction
The separation of test sample speckle and colour developing situation It is good to separate with the colour developing situation Color developing effect is bad
As can be seen from Table 4, reflux, extract, thin layer speckle effect is more effective than supersound extraction.
2, developing solvent consumption proportion preferred among the discrimination method B of the present invention:
Get need testing solution 5 μ l, point is on different silica gel g thin-layer plates, using petroleum ether (60-90 ℃)-ethyl acetate proportioning respectively is that 7.5: 0.3,8.5: 0.4,9.5: 0.5,10.5: 0.6,11.5: 0.7 developing solvent launches, take out, dry, put under the ultra-violet lamp and inspect, observe the unfolded effect of test sample speckle on each lamellae, the results are shown in following table:
Table 5 developing solvent consumption proportion optimization experiment result
The developing solvent proportioning 7.5∶0.3 ?8.5∶0.4 ?9.5∶0.5 ?10.5∶0.6 ?11.5∶0.7
Launch effect Very poor Difference Good Difference Very poor
Developing solvent proportioning as can be seen from Table 5 is 9.5: 0.5 o'clock, and it is best that need testing solution launches effect, phenomenons such as colour developing is unclear, the principal spot separation is bad, hangover occur.
3, sample solution point sample amount preferred among the discrimination method B of the present invention:
Get need testing solution 1 μ l, 2 μ l, 3 μ l, 4 μ l, 5 μ l, reference substance solution 5 μ l, point is on same silica gel g thin-layer plate, launch with the developing solvent that with petroleum ether (60-90 ℃)-ethyl acetate proportioning is 9.5: 0.5, take out, dry, put under the ultra-violet lamp and inspect, observe the effect of test sample principal spot colour developing on the lamellae, the results are shown in following table:
Table 6 sample solution point sample amount optimization experiment result
The point sample amount 2μl ?3μl ?4μl ?5μl
Effect Test sample is at corresponding reference substance position immaculate Test sample is very shallow in the colour developing of corresponding reference substance position speckle Test sample is shallow in the colour developing of corresponding reference substance position speckle Test sample is good at corresponding reference substance position speckle color developing effect
Test sample point sample amount is when 5 μ l as can be seen from Table 6, and color developing effect is good on lamellae, is fit to test requirements document.
4, negative control test
Get the negative sample that lacks Radix Angelicae Sinensis, prepare negative control solution, launch the back and corresponding fluorescence speckle on the reference substance solution correspondence position, do not occur, illustrate that selected identification experiment specificity is strong according to need testing solution preparation method among the above-mentioned discrimination method B.
The content assaying method test of experimental example 3 aconitines
Adopt high-efficient liquid phase technique to measure the content of the aconitine in the medicine of the present invention, to improve quality determining method of the present invention.
1, the selection of the extracting method of need testing solution
(1) investigation of extraction solvent amount:
Precision takes by weighing three parts of this product pharmaceutical preparatioies of the present invention, every part of 5g, and it is an amount of to add kieselguhr respectively, and mixing adds ether 30ml, 50ml, 100ml respectively, the preparation need testing solution.By method under the assay item need testing solution is detected.
Content with every gram medicine mesaconitine is that index determines to add the ether amount.Measurement result sees the following form:
Table 7 result of the test that adds diethyl ether
Figure A20071006406400151
Above result shows: the 50ml that adds diethyl ether, the every gram of 100ml gained medicine aconitine of the present invention content are basic identical, select the 50ml that adds diethyl ether according to actual needs for use.
(2) return time is investigated:
Precision takes by weighing three parts of medicines of the present invention, every part of 5g, and reflux, extract, is 30 minutes, 1 hour, 2 hours respectively, and the preparation need testing solution detects need testing solution by method under the assay item.
Content with every gram medicine mesaconitine is that index is determined extraction time.Measurement result sees the following form:
Table 8 return time result of the test
Figure A20071006406400152
Above result shows: the every gram of 1 hour extraction time, 2 hours gained medicine aconitine of the present invention content is basic identical, selects for use according to actual needs 1 hour.
2, the methodological study of content assaying method
To the detection method of content that medicine of the present invention adopted, carried out related side's science of law from aspects such as linear relationship, stability, precision, repeatability, the response rate and investigated, concrete outcome is as follows:
(1) linear relationship is investigated and is got reference substance solution (4mg → 50ml) shake up, accurate respectively 4,6,8,10,12, the 14 μ l of absorption inject high performance liquid chromatograph, measure peak area, the results are shown in following table, and drawing standard curve, show that aconitine is linear between 0.32 μ g-1.12 μ g, its regression equation is:
Area＝1250.08121*Amt-15.982788(r＝0.99965)
(2) stability test reference substance solution respectively at preparing the back 0,2,4,6,12,24 hour, is measured in accordance with the law, and the result shows that it is basicly stable in 24 hours, the results are shown in following table:
Table 9 stability test result
Figure A20071006406400162
(3) the accurate need testing solution 10 μ l that draw of precision test repeat sample introduction 5 times, try to achieve relative standard deviation＜2%, the results are shown in following table:
Table 10 Precision test result
Figure A20071006406400163
(4) the text method is pressed in repeatability test, gets five parts of the medicines of the present invention of same dosage form, and every part is measured, and tries to achieve relative standard deviation＜2%, the results are shown in following table:
Table 11 reproducible test results
Figure A20071006406400171
(5) the recovery test precision takes by weighing the medicine 2.5g of the present invention of the same dosage form of known content, and precision takes by weighing aconitine reference substance 0.50mg respectively again, presses the preparation method operation of need testing solution, measures its content, and calculates its response rate, and measurement result sees the following form:
Table 12 recovery test result
Figure A20071006406400172
From table 12 result of the test as can be seen, its linear relationship of the content assaying method that medicine of the present invention adopted, stability, precision, repeatability etc. are all good, can effectively control drug quality of the present invention.
Experimental example 4 medicines are to the influence of rat assist agent arthritis
Rat is divided into five groups promptly at random
Medicine group I (Radix Aconiti Preparata 40.25g, Radix Aconiti Kusnezoffii Preparata 70.25g, Radix Gentianae Macrophyllae 40.25g, Radix Angelicae Dahuricae 70.25g, Radix Glycyrrhizae 40.25g, Rhizoma Dioscoreae Hypoglaucae 120.5g, Rhizoma Dioscoreae Nipponicae 80.5g, Semen Coicis 120.5g, Rhizoma Arisaematis (processing) 40.25g, Flos Carthami 120.5g, Radix Angelicae Sinensis 40.25g, Radix Cynanchi Paniculati 185.75g)
Medicine group II (Radix Aconiti Preparata 45.25g, Radix Aconiti Kusnezoffii Preparata 65.25g, Radix Gentianae Macrophyllae 45.25g, Radix Angelicae Dahuricae 65.25g, Radix Glycyrrhizae 45.25g, Rhizoma Dioscoreae Hypoglaucae 115.5g, Rhizoma Dioscoreae Nipponicae 85.5g, Semen Coicis 115.5g, Rhizoma Arisaematis (processing) 45.25g, Flos Carthami 115.5g, Radix Angelicae Sinensis 45.25g, Radix Cynanchi Paniculati 175.75g)
Medicine group III (Radix Aconiti Preparata 53.25g, Radix Aconiti Kusnezoffii Preparata 53.25g, Radix Gentianae Macrophyllae 53.25g, Radix Angelicae Dahuricae 53.25g, Radix Glycyrrhizae 53.25g, Rhizoma Dioscoreae Hypoglaucae 106.5g, Rhizoma Dioscoreae Nipponicae 106.5g, Semen Coicis 106.5g, Rhizoma Arisaematis (processing) 53.25g, Flos Carthami 106.5g, Radix Angelicae Sinensis 53.25g, Radix Cynanchi Paniculati 159.75g)
Medicine group IV Radix Aconiti Preparata 53.25g, Radix Aconiti Kusnezoffii Preparata 53.25g, Radix Gentianae Macrophyllae 53.25g, Radix Angelicae Dahuricae 53.25g, Radix Glycyrrhizae 53.25g, Rhizoma Dioscoreae Hypoglaucae 106.5g, Rhizoma Dioscoreae Nipponicae 106.5g, Semen Coicis 106.5g, Rhizoma Arisaematis (processing) 53.25g, Flos Carthami 106.5g, Radix Paeoniae Alba 53.25g, Cortex Acanthopancis 159.75g
Medicine group I, medicine group II are compared the expelling wind and removing dampness effect with medicine group III respectively.Get 60 of rats, body weight 160 ± 20g, be divided into 3 groups at random, rat is injected in the right back foot pad with 0.05 milliliter of Freund ' s Freund's complete adjuvant under etherization, beginning drug treatment on the 8th, 3 times on the one, successive administration 15 days was observed 3 days after the drug withdrawal, observe different time foot swelling value, the results are shown in Table 13.
Table 13 medicine is to the influence of rat assist agent arthritis (X ± SD)
Group Dosage g/kg (only) 3h 2 days 8 days 10 days 12 days 15 days 18 days
Medicine group I 0.5 1.26± 0.39 0.98± 0.18 0.91± 0.25 0.90± 0.37 0.87± 0.24 0.82± 0.43 1.01± 0.41
Medicine group II 0.5 1.29± 0.29* 1.10± 0.31* 1.09± 0.28* 0.95± 0.35* 0.95± 0.27* 0.86± 0.37* 1.18± 0.25*
Medicine 0.5 1.35± 0.28* 1.18± 0.36* 1.10± 0.27* 0.98± 0.38* 0.97± 0.26* 0.92± 0.27* 1.26± 0.31*
Group III
Medicine group IV 0.5 1.25± 0.40 0.98± 0.15 0.93± 0.22 0.89± 0.39 0.85± 0.26 0.80± 0.41 1.05± 0.391
Annotate: * compares P＜0.05 with medicine group III
Table 13 is the result show: there were significant differences (P＜0.05) for pharmaceutical composition I of the present invention, II, IV capsule wind-damp dispelling function and medicine group III, medicine group I, II, IV to the influence of rat assist agent arthritis apparently higher than medicine III.
Experimental example 5 efficacy experiments
1, sex and age
Male's 239 examples, women's 261 examples minimum 16 years old, maximum 65 years old, are seen so that age group more 20-50 year.
2, the course of disease
The shortest person 25 days, elder 20 years, 3 years with interior at most, totally 500 examples.
Therapeutic Method: by specification is taken, the companion is a course of treatment moon, generally need to obey 2-3 the course of treatment, being divided into is two groups, medicine group IV (Radix Aconiti Preparata 53.25g of the present invention, Radix Aconiti Kusnezoffii Preparata 53.25g, Radix Gentianae Macrophyllae 53.25g, Radix Angelicae Dahuricae 53.25g, Radix Glycyrrhizae 53.25g Rhizoma Dioscoreae Hypoglaucae 106.5g, Rhizoma Dioscoreae Nipponicae 106.5g, Semen Coicis 106.5g, Rhizoma Arisaematis (processing) 53.25g, Flos Carthami 106.5g, Radix Paeoniae Alba 53.25g, Cortex Acanthopancis 159.75g) 200 examples, medicine group III (Radix Aconiti Preparata 53.25g of the present invention, Radix Aconiti Kusnezoffii Preparata 53.25g, Radix Gentianae Macrophyllae 53.25g, Radix Angelicae Dahuricae 53.25g, Radix Glycyrrhizae 53.25g Rhizoma Dioscoreae Hypoglaucae 106.5g, Rhizoma Dioscoreae Nipponicae 106.5g, Semen Coicis 106.5g, Rhizoma Arisaematis (processing) 53.25g, Flos Carthami 106.5g, Radix Angelicae Sinensis 53.25g, Radix Cynanchi Paniculati 159.75g) 200 example and control drug group (bony spur tablet) 100 examples.
3, curative effect determinate standard:
(1) clinical cure
Symptom all disappears, and it is normal that functional activity recovers, and main reference index (erythrocyte sedimentation rate, anti-chain 0, rheumatoid factor) is normal.
(2) produce effects
Symptomatology disappears or cardinal symptom is eliminated, and function of joint is recovered substantially, can participate in operate as normal and work, and main reference index (various physico-chemical examination) is normal substantially.Observed result:
Table 14 total effects statistics. analyze
Figure A20071006406400201
Of the present invention group and control drug group comparison P＜0.05
Table 14 result shows that medicine group III of the present invention and medicine group IV therapeutic effect of the present invention are remarkable, and effective percentage is respectively 93%, 93.5%, and cure rate is respectively 25.5%, 25.0%.
(3) course of treatment and curative effect are relatively
Table 15 curative effect and comparative analysis course of treatment table
Figure A20071006406400202
Figure A20071006406400211
Medicine group of the present invention and control drug group be P＜0.05 relatively
No matter table 15 result shows medicine group III of the present invention and medicine group IV of the present invention and matched group medicine relatively to primary disease therapeutic effect course of disease length, curative effect all is significantly increased.
(4) primary symptom index and curative effect are relatively
Table 16 primary symptom index and curative effect comparison sheet
Figure A20071006406400212
Of the present invention group and control drug group comparison P＜0.05
From table 16 treatment front and back symptom relative analysis, as seen medicine group III of the present invention and medicine group IV of the present invention and matched group medicine are relatively to eliminating arthralgia, alleviate red and swollen heat, all there is significant curative effect aspects such as recovery motion function, can make anti-0 and erythrocyte sedimentation rate descend or recover normal, the part rheumatoid factor test is turned out cloudy, and to erythema iris or scleroma person are arranged, the elimination effect is arranged.
4, side effect
This observation group 200 examples use this medicine all to have no side effect.
Following embodiment all can realize the described effect of above-mentioned experimental example
The specific embodiment
Embodiment 1
Radix Aconiti Preparata 40.25g, Radix Aconiti Kusnezoffii Preparata 70.25g, Radix Gentianae Macrophyllae 40.25g, Radix Angelicae Dahuricae 70.25g, Radix Glycyrrhizae 40.25g, Rhizoma Dioscoreae Hypoglaucae 120.5g, Rhizoma Dioscoreae Nipponicae 80.5g, Semen Coicis 120.5g, Rhizoma Arisaematis (processing) 40.25g, Flos Carthami 120.5g, Radix Angelicae Sinensis 40.25g, Radix Cynanchi Paniculati 185.75g
This pharmaceutical composition adds conventional adjuvant, makes pill by common process.
Embodiment 2
Radix Aconiti Preparata 45.25g, Radix Aconiti Kusnezoffii Preparata 65.25g, Radix Gentianae Macrophyllae 45.25g, Radix Angelicae Dahuricae 65.25g, Radix Glycyrrhizae 45.25g, Rhizoma Dioscoreae Hypoglaucae 115.5g, Rhizoma Dioscoreae Nipponicae 85.5g, Semen Coicis 115.5g, Rhizoma Arisaematis (processing) 45.25g, Flos Carthami 115.5g, Radix Angelicae Sinensis 45.25g, Radix Cynanchi Paniculati 175.75g
This pharmaceutical composition adds conventional adjuvant, makes tablet by common process.
Embodiment 3
Radix Aconiti Preparata 70.25g, Radix Aconiti Kusnezoffii Preparata 40.25g, Radix Gentianae Macrophyllae 70.25g, Radix Angelicae Dahuricae 40.25g, Radix Glycyrrhizae 70.25g, Rhizoma Dioscoreae Hypoglaucae 80.5g, Rhizoma Dioscoreae Nipponicae 120.5g, Semen Coicis 80.5g, Rhizoma Arisaematis (processing) 70.25g, Flos Carthami 80.5g, Radix Angelicae Sinensis 70.25g, Radix Cynanchi Paniculati 125.75g
This pharmaceutical composition adds conventional adjuvant, makes granule by common process.
Embodiment 4
Radix Aconiti Preparata 65.25g, Radix Aconiti Kusnezoffii Preparata 45.25g, Radix Gentianae Macrophyllae 65.25g, Radix Angelicae Dahuricae 45.250g, Radix Glycyrrhizae 65.25g, Rhizoma Dioscoreae Hypoglaucae 85.5g, Rhizoma Dioscoreae Nipponicae 115.25g, Semen Coicis 85.5g, Rhizoma Arisaematis (processing) 65.25g, Flos Carthami 85.5g, Radix Angelicae Sinensis 65.25g, Radix Cynanchi Paniculati 145.75g
This pharmaceutical composition adds conventional adjuvant, makes injection by common process.
Embodiment 5
Radix Aconiti Preparata 35.25g, Radix Aconiti Kusnezoffii Preparata 35.25g, Radix Gentianae Macrophyllae 75.25g, Radix Angelicae Dahuricae 75.25g, Radix Glycyrrhizae 35.25g, Rhizoma Dioscoreae Hypoglaucae 75.5g, Rhizoma Dioscoreae Nipponicae 125.5g, Semen Coicis 125.5g, Rhizoma Arisaematis (processing) 35.25g, Flos Carthami 75.5g, Radix Angelicae Sinensis 75.25g, Radix Cynanchi Paniculati 190.75g
This pharmaceutical composition adds conventional adjuvant, makes mixture by common process.
Embodiment 6
Radix Aconiti Preparata 53.25g, Radix Aconiti Kusnezoffii Preparata 53.25g, Radix Gentianae Macrophyllae 53.25g, Radix Angelicae Dahuricae 53.25g, Radix Glycyrrhizae 53.25g, Rhizoma Dioscoreae Hypoglaucae 106.5g, Rhizoma Dioscoreae Nipponicae 106.5g, Semen Coicis 106.5g, Rhizoma Arisaematis (processing) 53.25g, Flos Carthami 106.5g, Radix Angelicae Sinensis 53.25g, Radix Cynanchi Paniculati 159.75g
This pharmaceutical composition adds conventional adjuvant, makes capsule by common process.
Embodiment 7
Radix Aconiti Preparata 40.25g, Radix Aconiti Kusnezoffii Preparata 70.25g, Radix Gentianae Macrophyllae 40.25g, Radix Angelicae Dahuricae 70.25g, Radix Glycyrrhizae 40.25g, Rhizoma Dioscoreae Hypoglaucae 120.5g, Rhizoma Dioscoreae Nipponicae 80.5g, Semen Coicis 120.5g, Rhizoma Arisaematis (processing) 40.25g, Flos Carthami 120.5g, Radix Angelicae Sinensis 40.25g, Radix Cynanchi Paniculati 185.75g
More than 12 the flavor, the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 8 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 2 times, and each 2 hours, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 5 times of parts by volume, does distillate exist? cold preservation filters to separating out white crystals under the condition, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 8 times of parts by volume boils 2 times, each 2 hours, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.30 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the soft capsule of clinical acceptance.
Embodiment 8
Radix Aconiti Preparata 45.25g, Radix Aconiti Kusnezoffii Preparata 65.25g, Radix Gentianae Macrophyllae 45.25g, Radix Angelicae Dahuricae 65.25g, Radix Glycyrrhizae 45.25g, Rhizoma Dioscoreae Hypoglaucae 115.5g, Rhizoma Dioscoreae Nipponicae 85.5g, Semen Coicis 115.5g, Rhizoma Arisaematis (processing) 45.25g, Flos Carthami 115.5g, Radix Angelicae Sinensis 45.25g, Radix Cynanchi Paniculati 175.75g
More than 12 the flavor, the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 8 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 2 times, and each 2 hours, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 5 times of parts by volume, and distillate cold preservation under 2-10 ℃ of condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 8 times of parts by volume boils 2 times, each 2 hours, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.30 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the concentrated watered pill of clinical acceptance.
Embodiment 9
Radix Aconiti Preparata 70.25g, Radix Aconiti Kusnezoffii Preparata 40.25g, Radix Gentianae Macrophyllae 70.25g, Radix Angelicae Dahuricae 40.25g, Radix Glycyrrhizae 70.25g, Rhizoma Dioscoreae Hypoglaucae 80.5g, Rhizoma Dioscoreae Nipponicae 120.5g, Semen Coicis 80.5g, Rhizoma Arisaematis (processing) 70.25g, Flos Carthami 80.5g, Radix Angelicae Sinensis 70.25g, Radix Cynanchi Paniculati 125.75g
More than 12 the flavor, the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 8 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 2 times, and each 2 hours, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 5 times of parts by volume, and distillate cold preservation under 2-10 ℃ of condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 8 times of parts by volume boils 2 times, each 2 hours, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.30 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the tablet of clinical acceptance.
Embodiment 10
Radix Aconiti Preparata 65.25g, Radix Aconiti Kusnezoffii Preparata 45.25g, Radix Gentianae Macrophyllae 65.25g, Radix Angelicae Dahuricae 45.250g, Radix Glycyrrhizae 65.25g, Rhizoma Dioscoreae Hypoglaucae 85.5g, Rhizoma Dioscoreae Nipponicae 115.25g, Semen Coicis 85.5g, Rhizoma Arisaematis (processing) 65.25g, Flos Carthami 85.5g, Radix Angelicae Sinensis 65.25g, Radix Cynanchi Paniculati 145.75g
More than 12 the flavor, the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 8 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 1 time, and each 3 hours, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 5 times of parts by volume, and distillate cold preservation under 2-10 ℃ of condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 8 times of parts by volume boils 1 time, each 3 hours, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.25 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the powder of clinical acceptance.
Embodiment 11
Radix Aconiti Preparata 35.25g, Radix Aconiti Kusnezoffii Preparata 35.25g, Radix Gentianae Macrophyllae 75.25g, Radix Angelicae Dahuricae 75.25g, Radix Glycyrrhizae 35.25g, Rhizoma Dioscoreae Hypoglaucae 75.5g, Rhizoma Dioscoreae Nipponicae 125.5g, Semen Coicis 125.5g, Rhizoma Arisaematis (processing) 35.25g, Flos Carthami 75.5g, Radix Angelicae Sinensis 75.25g, Radix Cynanchi Paniculati 190.75g
More than 12 the flavor, the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 6 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 3 times, and each 1 hour, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 4 times of parts by volume, and distillate cold preservation under 2-10 ℃ of condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 6 times of parts by volume boils 3 times, each 1 hour, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.35 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the granule of clinical acceptance.
Embodiment 12
Radix Aconiti Preparata 53.25g, Radix Aconiti Kusnezoffii Preparata 53.25g, Radix Gentianae Macrophyllae 53.25g, Radix Angelicae Dahuricae 53.25g, Radix Glycyrrhizae 53.25g, Rhizoma Dioscoreae Hypoglaucae 106.5g, Rhizoma Dioscoreae Nipponicae 106.5g, Semen Coicis 106.5g, Rhizoma Arisaematis (processing) 53.25g, Flos Carthami 106.5g, Radix Angelicae Sinensis 53.25g, Radix Cynanchi Paniculati 159.75g
More than 12 the flavor, the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 8 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 2 times, and each 2 hours, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 6 times of parts by volume, and distillate cold preservation under 2-10 ℃ of condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 6 times of parts by volume boils 2 times, each 2 hours, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.28 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the capsule of clinical acceptance.
The method of quality control of embodiment 13 preparations of the present invention
Get embodiment 2 contents and carry out assay:
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica was filler: with 65: 35: 3: the methanol-water-chloroform of 0.2 ratio-triethylamine is a mobile phase; Detect wavelength 240nm, number of theoretical plate calculates by the aconitine peak and is not less than 1500;
The preparation of reference substance solution: it is an amount of that the aconitine reference substance decided in accurate title, adds methylene chloride and make the solution of 80 μ g/ml;
The preparation of need testing solution: precision takes by weighing the plain sheet powder of pharmaceutical composition tablet of the present invention 2.5g, and it is an amount of to add kieselguhr, and mixing adds ether 50ml, ammonia solution 2ml, and reflux, extract, 1 hour is put cold filtration, and with ether washing nozzle and residue, washing liquid is incorporated filtrate into; Filtrate is put and is added 15m l washing twice in the separatory funnel, merges water liquid, and the 20ml that adds diethyl ether washing discards water layer, merges ether, volatilizes ether,, adds methylene chloride to scale to the 5ml volumetric flask with the dichloromethane solution transfer, shakes up, promptly;
Assay method: above solution filters with 0.45 μ m microporous filter membrane, gets subsequent filtrate, and accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn measured promptly;
Pharmaceutical composition per unit tablet of the present invention contains Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata with aconitine C 34H 47NO 11Meter must not be less than 0.02mg.
The method of quality control of embodiment 14 preparations of the present invention
Getting embodiment 7 contents differentiates:
A, get medicinal composition soft capsule agent content 5g of the present invention, the 50ml that adds diethyl ether, jolting was left standstill 30 minutes, filtered the filtrate evaporate to dryness; Residue adds ethyl acetate 1ml dissolving; Other gets imperatorin, isoimperatorin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 4 μ l of above-mentioned two kinds of solution, to put respectively on same silica gel g thin-layer plate, the petroleum ether-ether with 3: 2 ratios in the time of 30～60 ℃ is developing solvent, is launching below 25 ℃, takes out, and dries, and puts under the 365nm uviol lamp and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get medicinal composition soft capsule agent content 56g of the present invention, the 30ml that adds diethyl ether, heating and refluxing extraction 30 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 0.5m l makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 1g, the 10ml that adds diethyl ether, and supersound process 10 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution; Put respectively on same silica gel g thin-layer plate, the petroleum ether-ethyl acetate with 9.5: 0.5 ratios in the time of 60～90 ℃ is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
The method of quality control of embodiment 15 preparations of the present invention
Getting embodiment 11 contents differentiates and assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica was filler: with 65: 35: 3: the methanol-water-chloroform of 0.2 ratio-triethylamine is a mobile phase; Detect wavelength 240nm, number of theoretical plate calculates by the aconitine peak and is not less than 1500;
The preparation of reference substance solution: it is an amount of that the aconitine reference substance decided in accurate title, adds methylene chloride and make the solution of 80 μ g/ml;
The preparation of need testing solution: precision takes by weighing medicament composition granule agent content 2.5g of the present invention, and it is an amount of to add kieselguhr, and mixing adds ether 50ml, ammonia solution 2ml, and reflux, extract, 1 hour is put cold filtration, and with ether washing nozzle and residue, washing liquid is incorporated filtrate into; Filtrate is put and is added 15ml washing twice in the separatory funnel, merges water liquid, and the 20ml that adds diethyl ether washing discards water layer, merges ether, volatilizes ether,, adds methylene chloride to scale to the 5ml volumetric flask with the dichloromethane solution transfer, shakes up, promptly;
Assay method: above solution filters with 0.45 μ m microporous filter membrane, gets subsequent filtrate, and accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn measured promptly;
Pharmaceutical composition per unit granule of the present invention contains Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata in aconitine C34H47NO11, must not be less than 0.02mg;
Discrimination method: A, get medicament composition granule agent content 5g of the present invention, the 50ml that adds diethyl ether, jolting was left standstill 30 minutes, filtered the filtrate evaporate to dryness; Residue adds ethyl acetate 1ml dissolving; Other gets imperatorin, isoimperatorin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 4 μ l of above-mentioned two kinds of solution, to put respectively on same silica gel g thin-layer plate, the petroleum ether-ether with 3: 2 ratios in the time of 30～60 ℃ is developing solvent, is launching below 25 ℃, takes out, and dries, and puts under the 365nm uviol lamp and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get medicament composition granule agent 6g of the present invention, the 30ml that adds diethyl ether, heating and refluxing extraction 30 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 1g, the 10ml that adds diethyl ether, and supersound process 10 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution; Put respectively on same silica gel g thin-layer plate, the petroleum ether-ethyl acetate with 9.5: 0.5 ratios in the time of 60～90 ℃ is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
Embodiment 16
Radix Aconiti Preparata 53.25g Radix Aconiti Kusnezoffii Preparata 53.25g Radix Gentianae Macrophyllae 53.25g Radix Angelicae Dahuricae 53.25g Radix Glycyrrhizae 53.25g Rhizoma Dioscoreae Hypoglaucae 106.5g Rhizoma Dioscoreae Nipponicae 106.5g Semen Coicis 106.5g Rhizoma Arisaematis (processing) 53.25g Flos Carthami 106.5g Radix Angelicae Sinensis 53.25g Radix Cynanchi Paniculati 159.75g
More than 12 the flavor, the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add water (transferring pH value with hydrochloric acid is 3-4) and decoct secondary, and each 2 hours, collecting decoction filtered filtrate for later use; Radix Cynanchi Paniculati adds the water distillation, and distillate cold preservation filters to separating out white crystals, the crystallization natural drying, standby, the five tastes such as filtrate and medicinal residues and all the other Flos Carthamis decoct with water twice, each two hours, collecting decoction filtered, filtrate and above-mentioned filtrate merge, and being condensed into relative density is the thick paste of 1.28～1.30 (50 ℃), add the fine powder of the above-mentioned Radix Angelicae Dahuricae etc., mixing, drying is ground into fine powder, add above-mentioned white crystals, mixing is made 1000, promptly.
[discriminating]
(1) get this product 5g, the 50ml that adds diethyl ether, jolting was left standstill 30 minutes, filtered the filtrate evaporate to dryness.Residue adds ethyl acetate 1ml dissolving.Other gets imperatorin, isoimperatorin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 4 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with petroleum ether (30-60 ℃)-ether (3: 2), launching below 25 ℃, take out, dry, put under the uviol lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
(2) get this product 6g, the 30ml that adds diethyl ether, heating and refluxing extraction 30 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 1g, the 10ml that adds diethyl ether, and supersound process 10 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution.According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution.Putting respectively on same silica gel g thin-layer plate, is developing solvent with petroleum ether (60-90 ℃)-ethyl acetate (9.5: 0.5), launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
[assay] according to high performance liquid chromatography, chromatographic condition was tested with system suitability, is filler with octadecylsilane chemically bonded silica: with methanol-water-chloroform-triethylamine (65: 35: 3: 0.2) be mobile phase; Detect wavelength 240nm.Number of theoretical plate calculates by the aconitine peak and is not less than 1500.
The preparation of reference substance solution: it is an amount of that the aconitine reference substance decided in accurate title, adds methylene chloride and make the solution of 80 μ g/ml.
The preparation of need testing solution: precision takes by weighing this product capsule 's content 2.5g, and it is an amount of to add kieselguhr, and mixing adds ether 50ml, ammonia solution 2ml, and reflux, extract, 1 hour is put cold filtration, and with ether washing nozzle and residue, washing liquid is incorporated filtrate into.Filtrate is put and is added 15ml washing twice in the separatory funnel, merges water liquid, and the 20ml that adds diethyl ether washing discards water layer, merges ether, volatilizes ether,, adds methylene chloride to scale to the 5ml volumetric flask with the dichloromethane solution transfer, shakes up, promptly.
The above solution of assay method filters with microporous filter membrane (0.45 μ m), gets subsequent filtrate, and accurate respectively absorption reference substance liquid, each 10 μ l of test sample liquid inject chromatograph of liquid, measure promptly.Every contains Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata with aconitine (C in this product 34H 47NO 11) meter, must not be less than 0.02mg.
Embodiment 17
Radix Aconiti Preparata 53.25g, Radix Aconiti Kusnezoffii Preparata 53.25g, Radix Gentianae Macrophyllae 53.25g, Radix Angelicae Dahuricae 53.25g, Radix Glycyrrhizae 53.25g, Rhizoma Dioscoreae Hypoglaucae 106.5g, Rhizoma Dioscoreae Nipponicae 106.5g, Semen Coicis 106.5g, Rhizoma Arisaematis (processing) 53.25g, Flos Carthami 106.5g, Radix Paeoniae Alba 53.25g, Cortex Acanthopancis 159.75g
This pharmaceutical composition adds conventional adjuvant, makes capsule by common process.
Embodiment 18
Radix Aconiti Preparata 40.25g, Radix Aconiti Kusnezoffii Preparata 70.25g, Radix Gentianae Macrophyllae 40.25g, Radix Angelicae Dahuricae 70.25g, Radix Glycyrrhizae 40.25g, Rhizoma Dioscoreae Hypoglaucae 120.5g, Rhizoma Dioscoreae Nipponicae 80.5g, Semen Coicis 120.5g, Rhizoma Arisaematis (processing) 40.25g, Flos Carthami 120.5g, Radix Paeoniae Alba 40.25g, Cortex Acanthopancis 185.75g
This pharmaceutical composition adds conventional adjuvant, makes pill by common process.
Embodiment 19
Radix Aconiti Preparata 45.25g, Radix Aconiti Kusnezoffii Preparata 65.25g, Radix Gentianae Macrophyllae 45.25g, Radix Angelicae Dahuricae 65.25g, Radix Glycyrrhizae 45.25g, Rhizoma Dioscoreae Hypoglaucae 115.5g, Rhizoma Dioscoreae Nipponicae 85.5g, Semen Coicis 115.5g, Rhizoma Arisaematis (processing) 45.25g, Flos Carthami 115.5g, Radix Paeoniae Alba 45.25g, Cortex Acanthopancis 175.75g
This pharmaceutical composition adds conventional adjuvant, makes tablet by common process.

Claims (10)

1. the rheumatismal pharmaceutical composition of treatment is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Aconiti Preparata 30-80 weight portion, Radix Aconiti Kusnezoffii Preparata 30-80 weight portion, Radix Gentianae Macrophyllae 30-80 weight portion, Radix Angelicae Dahuricae 30-80 weight portion, Radix Glycyrrhizae 30-80 weight portion, Rhizoma Dioscoreae Hypoglaucae 70-130 weight portion, Rhizoma Dioscoreae Nipponicae 70-130 weight portion, Semen Coicis 70-130 weight portion, Rhizoma Arisaematis (processing) 30-80 weight portion, Flos Carthami 70-130 weight portion, Radix Paeoniae Alba 30-80 weight portion, Cortex Acanthopancis 120-200 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that wherein Radix Paeoniae Alba 30-80 weight portion, Cortex Acanthopancis 120-200 weight portion substitute with following crude drug respectively: Radix Angelicae Sinensis 30-80 weight portion, Radix Cynanchi Paniculati 120-200 weight portion.
3. pharmaceutical composition as claimed in claim 2 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Aconiti Preparata 30-50 weight portion, Radix Aconiti Kusnezoffii Preparata 60-80 weight portion, Radix Gentianae Macrophyllae 30-50 weight portion, Radix Angelicae Dahuricae 60-80 weight portion, Radix Glycyrrhizae 30-50 weight portion, Rhizoma Dioscoreae Hypoglaucae 110-130 weight portion, Rhizoma Dioscoreae Nipponicae 70-90 weight portion, Semen Coicis 110-130 weight portion, Rhizoma Arisaematis (processing) 30-50 weight portion, Flos Carthami 110-130 weight portion, Radix Angelicae Sinensis 30-50 weight portion, Radix Cynanchi Paniculati 170-200 weight portion.
4. pharmaceutical composition as claimed in claim 3 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Aconiti Preparata 45.25 weight portions, Radix Aconiti Kusnezoffii Preparata 65.25 weight portions, Radix Gentianae Macrophyllae 45.25 weight portions, the Radix Angelicae Dahuricae 65.25 weight portions, Radix Glycyrrhizae 45.25 weight portions, Rhizoma Dioscoreae Hypoglaucae 115.5 weight portions, Rhizoma Dioscoreae Nipponicae 85.5 weight portions, Semen Coicis 115.5 weight portions, Rhizoma Arisaematis (processing) 45.25 weight portions, Flos Carthami 115.5 weight portions, Radix Angelicae Sinensis 45.25 weight portions, Radix Cynanchi Paniculati 175.75 weight portions.
5. pharmaceutical composition as claimed in claim 2 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Aconiti Preparata 51-59 weight portion, Radix Aconiti Kusnezoffii Preparata 51-59 weight portion, Radix Gentianae Macrophyllae 51-59 weight portion, Radix Angelicae Dahuricae 51-59 weight portion, Radix Glycyrrhizae 51-59 weight portion, Rhizoma Dioscoreae Hypoglaucae 100-109 weight portion, Rhizoma Dioscoreae Nipponicae 100-109 weight portion, Semen Coicis 100-109 weight portion, Rhizoma Arisaematis (processing) 51-59 weight portion, Flos Carthami 100-109 weight portion, Radix Angelicae Sinensis 51-59 weight portion, Radix Cynanchi Paniculati 155-165 weight portion.
6. pharmaceutical composition as claimed in claim 5 is characterized in that the crude drug of this pharmaceutical composition consists of: Radix Aconiti Preparata 53.25 weight portions, Radix Aconiti Kusnezoffii Preparata 53.25 weight portions, Radix Gentianae Macrophyllae 53.25 weight portions, the Radix Angelicae Dahuricae 53.25 weight portions, Radix Glycyrrhizae 53.25 weight portions, Rhizoma Dioscoreae Hypoglaucae 106.5 weight portions, Rhizoma Dioscoreae Nipponicae 106.5 weight portions, Semen Coicis 106.5 weight portions, Rhizoma Arisaematis (processing) 53.25 weight portions, Flos Carthami 106.5 weight portions, Radix Angelicae Sinensis 53.25 weight portions, Radix Cynanchi Paniculati 159.75 weight portions.
7. as the described preparation of drug combination method of claim 2-6, it is characterized in that this method is: above 12 flavors, the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 6-10 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 1-3 time, and each 1-3 hour, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 3-6 times of parts by volume, and distillate cold preservation under 2-10 ℃ of condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 6-10 times of parts by volume boils 1-3 time, each 1-3 hour, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.20～1.40 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the preparation of clinical acceptance.
8. preparation of drug combination method as claimed in claim 7 is characterized in that this method is: above 12 flavors, and the Radix Angelicae Dahuricae, Semen Coicis, Radix Angelicae Sinensis powder are broken into fine powder I; Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Radix Gentianae Macrophyllae add the water of 8 times of parts by volume, and transferring pH value with hydrochloric acid is 3～4, decoct 2 times, and each 2 hours, collecting decoction filtered, and it is standby to get filtrate I; Radix Cynanchi Paniculati adds the water distillation of 5 times of parts by volume, and distillate cold preservation under the 2-10 condition filters to separating out white crystals, get filtrate II, the crystallization natural drying, standby, the decocting that the five tastes such as filtrate II and medicinal residues and all the other Flos Carthamis is added 8 times of parts by volume boils 2 times, each 2 hours, collecting decoction filters, and gets filtrate II I, filtrate II I and filtrate I are merged, and relative density is 1.30 thick paste when being condensed into 50 ℃; Thick paste adds fine powder I, mixing, and drying is pulverized, and gets fine powder II, adds white crystals, adds conventional adjuvant again, through conventional method, makes the oral solid formulation of clinical acceptance.
9. as the method for quality control of the described pharmaceutical composition of claim 2-6, it is characterized in that this method of quality control comprises one or more in following discrimination method and/or the assay:
Assay: the test of chromatographic condition and system suitability: with octadecylsilane chemically bonded silica is filler: with 50-80: 20-50: 1-5: the methanol-water-chloroform of 0-0.5 ratio-triethylamine is a mobile phase; Detect wavelength 240nm, number of theoretical plate calculates by the aconitine peak and is not less than 1500;
The preparation of reference substance solution: it is an amount of that the aconitine reference substance decided in accurate title, adds methylene chloride and make the solution of 50-100 μ g/ml;
The preparation of need testing solution: precision takes by weighing the preparation content that is equivalent to crude drug content 1/60-1/125, and it is an amount of to add kieselguhr, mixing, add ether 50ml, ammonia solution 2ml, reflux, extract, 1 hour, put cold filtration, with ether washing nozzle and residue, washing liquid is incorporated filtrate into; Filtrate is put and is added 15ml washing twice in the separatory funnel, merges water liquid, and the 20ml that adds diethyl ether washing discards water layer, merges ether, volatilizes ether,, adds methylene chloride to scale to the 5ml volumetric flask with the dichloromethane solution transfer, shakes up, promptly;
Assay method: above solution filters with 0.45 μ m microporous filter membrane, gets subsequent filtrate, and accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn measured promptly;
Pharmaceutical composition per unit preparation of the present invention contains Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata with aconitine C 34H 47NO 11Meter must not be less than 0.02mg;
Discrimination method: A, get and be equivalent to crude drug content 1/30-1/65 preparation content, the 50ml that adds diethyl ether, jolting was left standstill 30 minutes, filtered the filtrate evaporate to dryness; Residue adds ethyl acetate 1ml dissolving; Other gets imperatorin, isoimperatorin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 4 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 2-4: the petroleum ether of 1-3 ratio (30～60 ℃)-ether is developing solvent, is launching below 25 ℃, takes out, and dries, and puts under the 365nm uviol lamp and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get the preparation content that is equivalent to crude drug content 1/25-1/55, the 30ml that adds diethyl ether, heating and refluxing extraction 30 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 1g, the 10ml that adds diethyl ether, and supersound process 10 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution; Put respectively on same silica gel g thin-layer plate, with 7.5-11.5: the petroleum ether of 0.3-0.7 ratio (60～90 ℃)-ethyl acetate is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
10. the method for quality control of pharmaceutical composition as claimed in claim 9 is characterized in that this method of quality control comprises one or more in following discrimination method and/or the assay:
Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica was filler: with 65: 35: 3: the methanol-water-chloroform of 0.2 ratio-triethylamine is a mobile phase; Detect wavelength 240nm, number of theoretical plate calculates by the aconitine peak and is not less than 1500;
The preparation of reference substance solution: it is an amount of that the aconitine reference substance decided in accurate title, adds methylene chloride and make the solution of 80 μ g/ml;
The preparation of need testing solution: precision takes by weighing gets the preparation content that is equivalent to crude drug content 1/120, and it is an amount of to add kieselguhr, and mixing adds ether 50ml, ammonia solution 2ml, and reflux, extract, 1 hour is put cold filtration, and with ether washing nozzle and residue, washing liquid is incorporated filtrate into; Filtrate is put and is added 15ml washing twice in the separatory funnel, merges water liquid, and the 20ml that adds diethyl ether washing discards water layer, merges ether, volatilizes ether,, adds methylene chloride to scale to the 5ml volumetric flask with the dichloromethane solution transfer, shakes up, promptly;
Assay method: above solution filters with 0.45 μ m microporous filter membrane, gets subsequent filtrate, and accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn measured promptly;
Pharmaceutical composition per unit preparation of the present invention contains Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata with aconitine C 34H 47NO 11Meter must not be less than 0.02mg;
Discrimination method: A, get the preparation content that is equivalent to crude drug content 1/60, the 50ml that adds diethyl ether, jolting was left standstill 30 minutes, filtered the filtrate evaporate to dryness; Residue adds ethyl acetate 1ml dissolving; Other gets imperatorin, isoimperatorin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 4 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with petroleum ether (30～60 ℃)-ether of 3: 2 ratios, launching below 25 ℃, take out, dry, put under the 365nm uviol lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get the preparation content that is equivalent to crude drug content 1/50, the 30ml that adds diethyl ether, heating and refluxing extraction 30 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 0.5ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 1g, the 10ml that adds diethyl ether, and supersound process 10 minutes filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution; Putting respectively on same silica gel g thin-layer plate, is developing solvent with petroleum ether (60～90 ℃)-ethyl acetate of 9.5: 0.5 ratios, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
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CN102648954A (en) * 2012-03-05 2012-08-29 韦小超 Medicament for treating rheumatism and processing method thereof
CN102908476A (en) * 2011-08-05 2013-02-06 支得福 Medicinal composition for treating rheumatoid arthritis
CN102920886A (en) * 2012-11-20 2013-02-13 天津大学 Medical composition for treating rheumatoid arthritis and preparation method
CN106198836A (en) * 2016-06-24 2016-12-07 中国人民解放军第三〇七医院 Clearing brain tablet method of quality control
CN106511830A (en) * 2016-12-06 2017-03-22 谭俊杰 Traditional Chinese medicine composition for treating arthropathy

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101856472A (en) * 2010-06-18 2010-10-13 中山市中智制药有限公司 Production method of spur pain-relieving capsule
CN101856472B (en) * 2010-06-18 2012-01-04 中山市中智制药有限公司 Production method of spur pain-relieving capsule
CN102908476A (en) * 2011-08-05 2013-02-06 支得福 Medicinal composition for treating rheumatoid arthritis
CN102908476B (en) * 2011-08-05 2014-05-28 支得福 Medicinal composition for treating rheumatoid arthritis
CN102648954A (en) * 2012-03-05 2012-08-29 韦小超 Medicament for treating rheumatism and processing method thereof
CN102920886A (en) * 2012-11-20 2013-02-13 天津大学 Medical composition for treating rheumatoid arthritis and preparation method
CN106198836A (en) * 2016-06-24 2016-12-07 中国人民解放军第三〇七医院 Clearing brain tablet method of quality control
CN106511830A (en) * 2016-12-06 2017-03-22 谭俊杰 Traditional Chinese medicine composition for treating arthropathy

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