CN101417020A

CN101417020A - Medicine composition capable of eliminating the mass and relieving swelling, absorbing clots and alleviating pain, preparation method and quality control method thereof

Info

Publication number: CN101417020A
Application number: CNA2007101762229A
Authority: CN
Inventors: 付立家; 付建家
Original assignee: Beijing Asia East Bio Pharmaceutical Co Ltd
Current assignee: Beijing Ya Dong Biological Pharmaceutical Co. Ltd. (Yasukuni)
Priority date: 2007-10-23
Filing date: 2007-10-23
Publication date: 2009-04-29
Anticipated expiration: 2027-10-23
Also published as: CN101417020B

Abstract

The invention discloses a pharmaceutical composition used for eliminating stagnation, reducing swelling, resolving blood stasis and relieving pain, and a preparation method and a quality control method thereof. The raw materials of the pharmaceutical composition consist of musk, semen momordicae (going through shelling and oil removal), prepared kusnezoff monkshood root, resin of sweetgum, frankincense (prepared), myrrh (prepared), excrementum pteropi (going through stir-heating with rice vinegar), angelica (going through stir-heating with liquor), earthworm and prepared ink. The preparation method comprises the steps: in the ten ingredients, except the artificial musk, other nine ingredients such as semen momordicae and the like are ground into fine powder; the artificial musk is porphyrized and matched with the fine powder; and the powder is sieved and directly prepared into clinically acceptable dose form by regular procedures or adding pharmaceutically acceptable inborn nature agents. The quality control method comprises the steps of carrying out microscopical identification to the medicine composition, carrying out thin-layer identification to the angelica, the frankincense and the earthworm, carrying out limit tests to aconitine in the kusnezoff monkshood root and carrying out content measurement to muscone in the musk. The pharmaceutical composition has very good effects of eliminating stagnation, reducing swelling, resolving blood stasis and relieving pain.

Description

Has mass dissipating and swelling eliminating, the pharmaceutical composition of blood-activating analgetic and preparation method and method of quality control

Invention field

The present invention relates to a kind of Chinese medicine composition, particularly have mass dissipating and swelling eliminating, the Chinese medicine composition of effect of dissolving stasis and relieving pain relates to the preparation method and the method for quality control of said composition simultaneously, belongs to technical field of Chinese medicines.

Background technology

Breast carcinoma is human modal a kind of malignant tumor, also is one of women's major malignant tumor.Estimate that according to American Cancer Society there is 120,000 breast carcinoma new cases every year in the U.S., sickness rate is that the number of dying from breast carcinoma in 72.2/10 ten thousand, 1976 is 33000.Breast carcinoma is in the sickness rate difference of China each department, though hanging down of China's genus women with breast cancer sent out a state in the world.But the sickness rate of breast carcinoma obviously increases in recent years.Especially Shanghai, capital, Tianjin and coastal area are the hotspots of China's breast carcinoma.The highest with Shanghai, the breast cancer incidence in Shanghai in 1972 be 20.1/10 ten thousand, 1988 be 28,/10 ten thousand then, occupy second in women's malignant tumor.

From traditional Chinese medical science angle, be born in the women more.Because of depressed rage impairing the liver, worry impairing spleen, so that stagnation of QI expectorant forms with fixed attention.Or dash wantonly two through lacking of proper care, qi stagnation hemagglutination and giving birth to.

Mostly adopt at present Comprehensive Treatment based on operation.Radical excision breast carcinoma is still the main means of breast cancer treatment.But the modern medicine viewpoint thinks that it promptly is a systemic disease that breast carcinoma idiopathy rises, and profile and the upper extremity function in order to preserve breast carried out multiple operation and integrated application radiotherapy, chemotherapy and Drug therapy less than the full milk excision simultaneously.And mammectomy and radiotherapy, chemotherapy all have certain limitation, and therefore, it is very necessary inventing a kind of medicine of conscientiously, effectively treating breast carcinoma.

Summary of the invention

One object of the present invention is to disclose a kind of new have mass dissipating and swelling eliminating, the Chinese medicine composition of effect of dissolving stasis and relieving pain; Another object of the present invention is to disclose a kind of new have mass dissipating and swelling eliminating, the preparation method of effect of dissolving stasis and relieving pain Chinese medicine composition; The object of the invention also is to disclose a kind of method of quality control of new Chinese medicine composition.

Of the present invention have a mass dissipating and swelling eliminating, and the Chinese medicine composition of effect of dissolving stasis and relieving pain is to be made by the crude drug of following weight ratio:

Moschus 8-20 weight portion, Semen Momordicae (shell and deoil) 80-100 weight portion, Radix Aconiti Kusnezoffii Preparata 80-100 weight portion, Herba Leonuri 80-100 weight portion, Olibanum (system) 30-50 weight portion, Herba Taraxaci 30-50 weight portion, Rhizoma Corydalis 80-100 weight portion, Radix Angelicae Sinensis (wine stir-fry) 30-50 weight portion, Pheretima 80-100 weight portion, XIANGMO(sic) 5-10 weight portion;

The above-mentioned raw materials optimum ratio is:

Moschus 10 weight portions, Semen Momordicae (shell and deoil) 90 weight portions, Radix Aconiti Kusnezoffii Preparata 90 weight portions, Herba Leonuri 90 weight portions, Olibanum (system) 40 weight portions, Herba Taraxaci 40 weight portions, Rhizoma Corydalis 90 weight portions, Radix Angelicae Sinensis (wine stir-fry) 40 weight portions, Pheretima 90 weight portions, XIANGMO(sic) 8 weight portions;

Of the present invention have a mass dissipating and swelling eliminating, and the Chinese medicine composition of effect of dissolving stasis and relieving pain can be made by the crude drug of following weight ratio:

Moschus 8-20 weight portion, Semen Momordicae (shell and deoil) 80-100 weight portion, Radix Aconiti Kusnezoffii Preparata 80-100 weight portion, Resina Liquidambaris 80-100 weight portion, Olibanum (system) 30-50 weight portion, Myrrha (processed) 30-50 weight portion, Oletum Trogopterori (vinegar stir-fry) 80-100 weight portion, Radix Angelicae Sinensis (wine stir-fry) 30-50 weight portion, Pheretima 80-100 weight portion, XIANGMO(sic) 5-10 weight portion;

The above-mentioned raw materials optimum ratio is:

Moschus 10 weight portions, Semen Momordicae (shell and deoil) 90 weight portions, Radix Aconiti Kusnezoffii Preparata 90 weight portions, Resina Liquidambaris 90 weight portions, Olibanum (system) 40 weight portions, Myrrha (processed) 40 weight portions, Oletum Trogopterori (vinegar stir-fry) 90 weight portions, Radix Angelicae Sinensis (wine stir-fry) 40 weight portions, Pheretima 90 weight portions, XIANGMO(sic) 8 weight portions;

The above-mentioned raw materials optimum ratio can also for:

Moschus 12 weight portions, Semen Momordicae (shell and deoil) 88 weight portions, Radix Aconiti Kusnezoffii Preparata 88 weight portions, Resina Liquidambaris 40 weight portions, Olibanum (system) 30 weight portions, Myrrha (processed) 37.5 weight portions, Oletum Trogopterori (vinegar stir-fry) 90 weight portions, Radix Angelicae Sinensis (wine stir-fry) 30 weight portions, Pheretima 40 weight portions, XIANGMO(sic) 5 weight portions;

Compositions of the present invention technology adding adjuvant is routinely made clinical acceptable forms such as tablet, capsule, oral liquid, drop pill, spray, granule; Described adjuvant comprises solvent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent, lubricant, substrate etc.

The preparation method of Chinese medicine composition pill of the present invention is:

Choose crude drug:

Method for making: above ten flavors, except that the artificial Moschus, nine flavors such as all the other Semen Momordicaes are ground into fine powder, with artificial Moschus's porphyrize, with above-mentioned powder facing-up, sieve.Every 100g powder adds starch 25g, mixing, and in addition with starch 5g system 14% starch slurry, general ball, dry below 80 ℃, promptly.

Choose crude drug: Moschus 8-20 weight portion, Semen Momordicae (shell and deoil) 80-100 weight portion, Radix Aconiti Kusnezoffii Preparata 80-100 weight portion, Herba Leonuri 80-100 weight portion, Olibanum (system) 30-50 weight portion, Herba Taraxaci 30-50 weight portion, Rhizoma Corydalis 80-100 weight portion, Radix Angelicae Sinensis (wine stir-fry) 30-50 weight portion, Pheretima 80-100 weight portion, XIANGMO(sic) 5-10 weight portion;

Described parts by volume/weight portion is corresponding with ml/g.

The method of quality control of Chinese medicine composition of the present invention comprises discriminating and/or assay and/or inspection.Discrimination method comprises a kind of and/or several in the following method:

(1) it is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, take by weighing to be equivalent to crude drug 3-4g, and the 10-30ml that adds diethyl ether, supersound process 10-30 minute, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (7-9:1-3) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

(2) get Olibanum control medicinal material 0.1g, the 1ml that adds diethyl ether flooded 1-3 hour, and supernatant is medical material solution in contrast.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each the 5 μ l of need testing solution under control medicinal material solution and discriminating (1) item, put respectively on same silica gel g thin-layer plate, with petroleum ether (60-90 ℃)-ethyl acetate (90-100:0-10) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.

(3) it is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, takes by weighing to be equivalent to crude drug 3-4g, add the ethanol 40-60ml of 60-80%, placement is spent the night, and filters, filtrate is steamed to there not being the ethanol flavor, add water 10-30ml dissolving, use chloroform extraction 1-3 time, each 10-30ml, merge chloroform liquid, evaporate to dryness, residue is with methanol 2ml dissolving, as need testing solution.Other gets Pheretima control medicinal material 1g, shines medical material solution in pairs with legal system.According to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel H lamellae, with cyclohexane extraction-ethyl acetate (8-10:0-2) is developing solvent, launches twice, takes out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

Assay comprises following method:

Measure according to gas chromatography (2005 editions one appendix VI E of Chinese Pharmacopoeia).Chromatographic condition and system suitability test are immobile phase with silicone (OV-17), and coating concentration is 5%; 190 ℃ of column temperatures, 220 ℃ of injector temperatures, 240 ℃ of detector temperatures are carrier gas with nitrogen.Number of theoretical plate calculates by the muscone peak should be not less than 1500.It is an amount of that correction factor mensuration is got AI3-36122, and accurate the title decides, and adds cyclohexane extraction and makes the solution that every 1ml contains 0.2mg, as inner mark solution.It is an amount of that other gets the muscone reference substance, and accurate the title decides, and adds cyclohexane extraction and makes the solution that every 1ml contains 0.2mg, in contrast the product storing solution.Above two kinds of each 2ml of solution of accurate absorption put in the measuring bottle of same 10ml, add cyclohexane extraction and are diluted to scale, shake up, in contrast product solution.Draw reference substance solution 2 μ l, inject gas chromatograph, the calculation correction factor.

Assay method is got pharmaceutical preparation of the present invention, is ground into fine powder, gets powder and is equivalent to crude drug 0.5-1.5g, and accurate the title decides, mark liquid 2ml in accurate the adding, cyclohexane extraction 8ml, close plug, jolting, ultrasonic 20-40min filters, the accurate subsequent filtrate 2 μ l that draw, inject gas chromatograph calculates, promptly.

Of the present invention pharmaceutical preparation suitable with the 0.77g crude drug contains the artificial Moschus with muscone (C ₁₆H ₃₀O) calculate, must not be less than 0.3mg.

Inspection comprises following method:

It is an amount of that aconitine limit is got pharmaceutical composition of the present invention, is ground into fine powder, takes by weighing to be equivalent to crude drug 7-8g, put in the conical flask, add ammonia solution 10ml, mix thoroughly, placed 1-3 hour, and added absolute ether 100-150ml, jolting 0.5-2 hour, placed 12-36 hour, filter, filtrate adds hydrochloric acid solution (4 → 100) jolting and extracts 3 (15-25ml, 10-20ml, 10-20ml), merge hydrochloric acid solution, hydrochloric acid solution adds strong ammonia solution, transfers Ph value to 9～10, adding the absolute ether jolting extracts 3 times, each 15-25ml merges ether solution, volatilizes, residue adds dehydrated alcohol 1ml makes dissolving, as need testing solution.Other gets the aconitine reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw need testing solution 15 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with benzene-ethyl acetate-diethylamine (5-10:1-3:0.5-2) is developing solvent, presaturation launched after 2 hours, take out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of appearance should or speckle not occur less than the speckle of reference substance.

The present composition has good effect at mass dissipating and swelling eliminating on the blood-activating analgetic, said composition toxicity is very little, and clinical practice is safe and reliable.Radix Aconiti Kusnezoffii Preparata dispelling cold by warming the meridian, channels-freeing dampness-dispelling in the side are monarch drug.Pheretima invigorate blood circulation dysmenorrhea, Semen Momordicae vanishing sputum and dispelling knot, Radix Angelicae Sinensis, Oletum Trogopterori, Olibanum, Myrrha promoting blood circulation to remove blood stasis are ministerial drug altogether.Assistant is with Resina Liquidambaris, XIANGMO(sic) subduing swelling and detoxicating, and the hot perfume (or spice) of Moschus is walked string, promoting the flow of QI in the collateral by warming the meridian, the detoxifcation pain relieving.All medicines share, and play the effect of mass dissipating and swelling eliminating, blood-activating analgetic altogether.

Present composition preparation has stronger mass dissipating and swelling eliminating, effect of dissolving stasis and relieving pain, and can be by improving S ₁₈₀Mice ear microcirculation, reduction mice with tumor whole blood viscosity suppress tumor growth, the effect of unrestraint weight of mice.

Present composition preparation production technique advanced person, method of quality control can carry out effective and stable control to the quality of product.Following experimental example is used to further specify the present invention.

The research of experimental example 1 technological experiment

1, smashing fineness test

Press recipe quantity configuration medical material, every part contains Moschus 10g, Semen Momordicae (shell and deoil) 90g, Radix Aconiti Kusnezoffii Preparata 90g, Resina Liquidambaris 90g, Olibanum (system) 40g, Myrrha (processed) 40g, Oletum Trogopterori (vinegar stir-fry) 90g, Radix Angelicae Sinensis (wine stir-fry) 40g, Pheretima 90g, XIANGMO(sic) 8g, divide four groups to do experiment respectively: smashing fineness is respectively: 50 orders, 65 orders, 80 orders, 100 orders are that index is determined smashing fineness with pill viscosity, pill outward appearance, pulverizing loss respectively.The results are shown in Table 1:

Table 1: pulverize result of the test

Above result shows: when smashing fineness was 80 orders, every index was better, so select 80 orders for use in producing.

2, starch amount of water test

Press the recipe quantity configuration, get respective amount starch and divide four groups to experimentize, 2 times of amounts of first group of amount of water, 4 times of amounts of second group of amount of water, 6 times of amounts of the 3rd group of amount of water, 8 times of amounts of the 4th group of amount of water are that index is determined amount of water with pill viscosity, pill outward appearance, drying time respectively.The results are shown in Table 2,

Table 2: amount of water result of the test

With pill viscosity, pill outward appearance is index, and pill viscosity is better when adding 6 times of amounts of water as can be seen, selects the 6 times of amounts of water that add in the production for use.

Table 3: three batches of pilot scale creation datas

Experimental example 2 discrimination method experimentatioies

1. Radix Angelicae Sinensis discrimination test screening

(1) preparation of need testing solution

Method one: get pharmaceutical preparation of the present invention and be equivalent to crude drug 3.85g, porphyrize, the 20ml that adds diethyl ether, supersound process 10 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.

Method two: get pharmaceutical preparation of the present invention and be equivalent to crude drug 3.85g, porphyrize, the 20ml that adds diethyl ether, supersound process 20 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.

Method three: get pharmaceutical preparation of the present invention and be equivalent to crude drug 3.85g, porphyrize, the 20ml that adds diethyl ether, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.

Other gets Radix Angelicae Sinensis control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each 5 μ l of above-mentioned three kinds of need testing solutions and control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (9:1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

	The clear spot degree	The hangover situation	Disturbed condition
	The clear spot degree	The hangover situation	Disturbed condition	Method one	Unintelligible	Do not have	Do not have
Method two:	Clear	Do not have	Do not have	Method one	Unintelligible	Do not have	Do not have
Method two:	Clear	Do not have	Do not have	Method three:	Clear	Do not have	Do not have

(2) developing solvent proportioning preferred:

Developing solvent one: normal hexane-ethyl acetate (7:3) is developing solvent

Developing solvent two: normal hexane-ethyl acetate (8:2) is developing solvent

Developing solvent three: normal hexane-ethyl acetate (9:1) is developing solvent

It is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, and take by weighing preparation and be equivalent to crude drug 3.85g, the 10-30ml that adds diethyl ether, supersound process 10-30 minute, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, developing solvent one, two, three, launch respectively, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

	The clear spot degree	The hangover situation	Disturbed condition
	The clear spot degree	The hangover situation	Disturbed condition	Developing solvent one	Unintelligible	Do not have	Do not have
Developing solvent two:	Clear	Do not have	Have	Developing solvent one	Unintelligible	Do not have	Do not have
Developing solvent two:	Clear	Do not have	Have	Developing solvent three:	Clear	Do not have	Do not have

When developing solvent is 9:1 as can be seen from the above table, launch effectively on lamellae, principal spot is clear, does not have hangover, and is identical with the speckle displacement and the color of reference substance, is fit to test requirements document.

(3) sample solution point sample amount is preferred:

It is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, and take by weighing preparation and be equivalent to crude drug 3.85g, the 10-30ml that adds diethyl ether, supersound process 10-30 minute, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw above-mentioned two kinds of solution each 1 μ l, 3 μ l, 5 μ l, 10 μ l respectively, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (9:1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

Sample solution point sample amount optimization experiment is table as a result

The point sample amount	1 μ l	3 μ l	5 μ l	10 μ l
The point sample amount	1 μ l	3 μ l	5 μ l	10 μ l	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 identical in corresponding reference substance position spot colors	Test sample is identical in corresponding reference substance position spot colors, but hangover is arranged slightly.

Test sample point sample amount is when 5 μ l as can be seen from the above table, and color developing effect is good on lamellae, is fit to test requirements document.

2. Olibanum discrimination test screening

(1) developing solvent proportioning preferred:

Developing solvent one: petroleum ether (60-90 ℃)-ethyl acetate (90:10);

Developing solvent two: petroleum ether (60-90 ℃)-ethyl acetate (95:5);

Developing solvent three: petroleum ether (60-90 ℃);

Get Olibanum control medicinal material 0.1g, the 1ml that adds diethyl ether flooded 1 hour, and supernatant is medical material solution in contrast.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each the 5 μ l of need testing solution under control medicinal material solution and discriminating (2) item, put respectively on same silica gel g thin-layer plate, with developing solvent one, two, three, launch respectively, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.

	The clear spot degree	The hangover situation	Disturbed condition
	The clear spot degree	The hangover situation	Disturbed condition	Developing solvent one	Clear	Do not have	Have

Developing solvent two:	Clear	Do not have	Do not have
Developing solvent two:	Clear	Do not have	Do not have	Developing solvent three:	Clear	Do not have	Do not have

It is clear that above as can be seen from the above table developing solvent two, three all develops the color, and do not have hangover, but consider that the simple preferred developing solvent of technology is petroleum ether (60-90 a ℃).

(2) sample solution point sample amount is preferred:

3. Pheretima discrimination test screening

(1) preparation of need testing solution

The selection of extractant

Extractant one: chloroform

Extractant two: normal hexane

Extractant three: n-butyl alcohol

It is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, takes by weighing preparation and is equivalent to crude drug 3.08g, add 70% ethanol 50ml, placement is spent the night, and filters, filtrate is steamed to there not being the ethanol flavor, adds water 20ml dissolving, uses extractant one, two, three respectively, extraction is secondary altogether, each 20ml merges chloroform liquid, evaporate to dryness, residue is with methanol 2ml dissolving, as need testing solution.

Other gets Pheretima control medicinal material 1g, shines medical material solution in pairs with legal system.According to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel H lamellae, with cyclohexane extraction-ethyl acetate (9:1) is developing solvent, launches twice, takes out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

The result

	Launch effect	The forward position	Hangover	Disturb
	Launch effect	The forward position	Hangover	Disturb	Extraction one	Clear spot	Do not have	Do not have	Do not have
Extraction two	Immaculate	—	—	—	Extraction one	Clear spot	Do not have	Do not have	Do not have
Extraction two	Immaculate	—	—	—	Extraction three	Clear spot	Do not have	Do not have	Have

(2) developing solvent proportioning preferred:

Developing solvent one: cyclohexane extraction-ethyl acetate (8:2);

Developing solvent two: cyclohexane extraction-ethyl acetate (9:1);

Developing solvent three: cyclohexane extraction

It is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, takes by weighing preparation and is equivalent to crude drug 3.08g, add 70% ethanol 50ml, placement is spent the night, and filters, filtrate is steamed to there not being the ethanol flavor, add water 20ml dissolving, use chloroform extraction 2 times, each 20ml, merge chloroform liquid, evaporate to dryness, residue is with methanol 2ml dissolving, as need testing solution.Other gets Pheretima control medicinal material 1g, shines medical material solution in pairs with legal system.According to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel H lamellae, with developing solvent one, two, three, launch twice respectively, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

	The clear spot degree	The hangover situation	Disturbed condition
	The clear spot degree	The hangover situation	Disturbed condition	Developing solvent one	Clear	Do not have	Have
Developing solvent two:	Clear	Do not have	Do not have	Developing solvent one	Clear	Do not have	Have
Developing solvent two:	Clear	Do not have	Do not have	Developing solvent three:	Clear	Have	Do not have

When developing solvent is cyclohexane extraction-ethyl acetate (9:1) as can be seen from the above table, launch effectively on lamellae, principal spot is clear, does not have hangover, and is identical with the speckle displacement and the color of reference substance, is fit to test requirements document.

(3) sample solution point sample amount is preferred:

It is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, takes by weighing preparation and is equivalent to crude drug 3.08g, add 70% ethanol 50ml, placement is spent the night, and filters, filtrate is steamed to there not being the ethanol flavor, add water 20ml dissolving, use chloroform extraction 2 times, each 20ml, merge chloroform liquid, evaporate to dryness, residue is with methanol 2ml dissolving, as need testing solution.Other gets Pheretima control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (2005 editions appendix VIB of Chinese Pharmacopoeia), draw above-mentioned two kinds of solution each 1 μ l, 3 μ l, 5 μ l, 10 μ l, put respectively on same silica gel H lamellae, with cyclohexane extraction-ethyl acetate (9:1) is developing solvent, launch twice, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

The point sample amount	The clear spot degree	The hangover situation	Disturbed condition
The point sample amount	The clear spot degree	The hangover situation	Disturbed condition	1μl	Unintelligible	Do not have	Do not have
3μl	The principal spot very slight color	Do not have	Do not have	1μl	Unintelligible	Do not have	Do not have
3μl	The principal spot very slight color	Do not have	Do not have	5μl	Color is clear	Do not have	Do not have
10μl	Color is clear	Have	Do not have	5μl	Color is clear	Do not have	Do not have

Experimental example 3 is checked an experimentation

The research of heavy metal and arsenic salt

1 heavy metal inspection

Assay method: get this product fine powder 2g, put in the crucible, low-temperature carbonization, to 600 ℃ of complete ashing, its residue adds hydrochloric acid 2ml again, and water bath method adds water 15ml, checks (an appendix IX of Chinese Pharmacopoeia version in 2005 E second method) in accordance with the law.Altogether the heavy metal limit of three batch samples is checked that by assay method content is all less than 10ppm, so exclude text.The results are shown in Table 1.

The heavy metal check result of table 1 three batch samples

2 arsenic salt are checked

Assay method:

The preparation of standard arsenic speckle: press first method operation under an appendix IX of Chinese Pharmacopoeia version in 2005 the F item, accurate absorption standard arsenic solution 2ml, preparation in accordance with the law.

Test sample is measured: get this product fine powder 1g, put low-temperature heat carbonization in the crucible, put coldly, blazingly make ashing gradually at 600 ℃, put cold, add 10% ammonium nitrate solution and make residue moistening, put evaporate to dryness in the water-bath then, residue is blazing to ashing fully at 600 ℃ again, put cold, add hydrochloric acid 5ml, add water 23ml and move in the survey arsenic bottle, according to " preparation of standard arsenic speckle " inspection down.

By the preparation method of arsenic salt inspection under the assay method item arsenic salt of three batch samples is limited the quantity of and to check that content is all less than 2ppm, so exclude text.The results are shown in Table 2.

The arsenic salt check result of table 2 three batch samples

Aconitine limit is checked

The standard substance source: the aconitine reference substance is purchased lot number: the 720-200208 in Nat'l Pharmaceutical ﹠ Biological Products Control Institute

This is the limit examine of Radix Aconiti Kusnezoffii Preparata mesaconitine, uses silica gel g thin-layer plate, is developing solvent with benzene-ethyl acetate-diethylamine (7:2:0.5), launches, and takes out, and dries, and spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of appearance is less than the speckle of reference substance.

Experimental example 4 assay experimental studies

The muscone assay

Detecting instrument: Agilent gas phase 4890 chromatographs

Chromatographic column: silicone (OV-17) coating concentration is 5%

Carrier gas: nitrogen

Detector temperature: 240 ℃ of injector temperatures: 220 ℃ of column temperatures: 190 ℃

Reference substance: muscone

Internal standard substance: AI3-36122

Assay method: it is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, takes by weighing preparation and is equivalent to crude drug 0.77g, accurate claim fixed, mark liquid 2ml in accurate the adding, cyclohexane extraction 8ml, close plug, jolting, ultrasonic 30min filters, the accurate subsequent filtrate 2 μ l that draw, inject gas chromatograph calculates, promptly;

Artificial Moschus's blank sample preparation: get Semen Momordicae (shell and deoil) 90g, Radix Aconiti Kusnezoffii Preparata 90g, Resina Liquidambaris 90g, Olibanum (system) 40g, Myrrha (processed) 40g, Oletum Trogopterori (vinegar stir-fry) 90g, Radix Angelicae Sinensis (wine stir-fry) 40g, Pheretima 90g, XIANGMO(sic) 8g nine and distinguish the flavor of and be ground into fine powder, sieve.Every 100g powder adds starch 25g, mixing, and in addition with starch 5g system magma, general ball, cold drying, promptly; The negative controls preparation: get artificial Moschus's blank sample, be ground into fine powder, get powder 1g, the accurate title, decide, mark liquid 2ml in accurate the adding, and cyclohexane extraction 8ml, close plug, jolting, ultrasonic 30min, filtration is got subsequent filtrate, promptly.

1. content assaying method is investigated:

(1) stability test

Get reference substance solution (muscone 0.049948mg/ml, AI3-36122 0.0415mg/ml), respectively at 0,4,8,12, the 24 hour sample introduction 2ul in preparation back, measure in accordance with the law, the result shows that it is basicly stable in 24 hours, the results are shown in following table

(2) linear relationship is investigated

Ratio with peak area is a vertical coordinate, and the reference substance sample size is an abscissa, and the drawing standard curve gets regression equation Y=22.7364X+0.0167 (r=0.99945)

(3) precision test

Accurate reference substance solution (muscone concentration is that 0.024974mg/ml, AI3-36122 concentration are 0.0415mg/ml) the 2 μ l that draw repeat sample introduction 5 times, try to achieve relative standard deviation＜2%, the results are shown in following table

(4) repeatability test

Press the text method, get 5 parts in same lot number sample, every part is measured, try to achieve relative standard deviation＜2%, the results are shown in following table

(5) recovery test sample thief 0.5g, accurate title is fixed, accurate muscone solution (0.24974mg/ml) 1ml that adds, mark liquid 2ml in the accurate again adding, cyclohexane extraction 7ml measures its content by the text method, and calculates its response rate, and measurement result sees the following form:

2. assay result:

Lot number	Content (mg/g)
Lot number	Content (mg/g)	051222101	0.4625
051222202	0.4587	051222101	0.4625
051222202	0.4587	051222303	0.4421

According to above data, content limit is decided to be: the every 1g of this product contains the artificial Moschus in muscone, must not be less than 0.3mg.

Experimental example 5 pharmacodynamic experiments

Experimental technique

1, experiment medicine

(1) Hai Pu pharmaceutical factory in 5-FU Shanghai produces.

(2) medicine group of the present invention: Moschus 10g, Semen Momordicae (shell and deoil) 50g, Radix Aconiti Kusnezoffii Preparata 50g, Resina Liquidambaris 50g, Olibanum (system) 25g, Myrrha (processed) 25g, Oletum Trogopterori (vinegar stir-fry) 50g, Radix Angelicae Sinensis (wine stir-fry) 25g, Pheretima 50g, XIANGMO(sic) 4g.

[method for making] above ten flavors, except that the artificial Moschus, nine flavors such as all the other Semen Momordicaes are ground into fine powder, with artificial Moschus's porphyrize, with above-mentioned powder facing-up, sieve.Every 100g powder adds starch 25g, mixing, and in addition with starch 5g system 14% starch slurry, general ball, dry below 80 ℃, promptly.

(3) the Chinese medicine side of contrast XIAOJIN WAN is commercially available.

2, experimental technique

(1) inoculates under the aseptic condition S ₁₈₀The size into about 2 * 2 * 2mm is cut apart in the tumor strain, and being inoculated in the right front axil of kunming mice, subcutaneous (hereinafter to be referred as this Mus is S ₁₈₀Mice).

(2) grouping is inoculated back second day with S ₁₈₀Mice is divided into 4 groups at random; 20 of medicine groups of the present invention, 18 of Chinese medicine matched groups, 5-FU group 19 only reaches S ₁₈₀30 of mice matched groups.Establish 33 of one group of normal mouse matched groups in addition again.

For the demonstration test result, this experiment successively repeats twice with same method.Therefore, above-mentioned laboratory animal is divided into two batches at random and experimentizes.

(3) administration medicine group of the present invention oral bolus of drug of the present invention every day, the suitable crude drug of dosage is the 0.03g/10g body weight, the Chinese medicine matched group oral Chinese medicine every day side of contrast granule, the suitable crude drug of dosage is the 0.03g/10g body weight; 5-FU group lumbar injection 5-FU injection every day, dosage is the 0.25mg/10g body weight; S ₁₈₀Mice matched group and normal group mice then every day oral normal saline 0.4ml, 10 days courses of treatment.

Through pharmacology toxicity test medicine LD of the present invention ₅₀Be 42.3g/kg, the Chinese medicine side of contrast LD ₅₀Be 41.1g/kg.

1. microcirculation (ear) room temperature is 20 ℃, after the anesthesia, and with the blood flow rate of biology microscope sem observation auricle portion small artery, venule and blood capillary, and with oscillograph (SBD _-6) record.

Result: microcirculation (ear) normal group mice and S ₁₈₀Ear's microcirculation observed result before the mice matched group is dead, the blood flow rate of normal mouse small artery, venule and blood capillary is respectively 0.647 ± 0.131mm/s, 0.610 ± 0.078mm/s and 0.672 ± 0.046mm/s, and S ₁₈₀The mice matched group then is respectively 0.394 ± 0.047mm/s, 0.249 ± 0.048mm/s and 0.264 ± 0.089mm/s, and both have highly significant difference.Be limited to condition, do not observe the microcirculation of other group mice.

2. whole blood viscosity cone and plate viscometer (NEX-1).

The result: the whole blood viscosity measurement result saw Table 1 before each group mice of whole blood viscosity was put to death.Under low shear rate (46r/min), the blood viscosity of normal group mice is starkly lower than S ₁₈₀Mice matched group and Chinese medicine matched group.(under the 230r/min, each organizes mice blood viscosity no significant difference (P＜0.05), sees Table 1 at high shear rate.

Table 1: each experimental mice whole blood viscosity mensuration (unit: pool gram x ± SD)

Each group of low shear rate is compared P＜0.05 with normal group; The 5-FU group compares P＜0.05 with the S180 matched group;

Medicine group of the present invention and Chinese medicine matched group compare, P＜0.05

Each group of high shear rate compares no significant difference P with normal group〉0.05

3. isolate tumor behind the heavy sacrifice of animal of tumor, peplos around rejecting claims weight in wet base immediately.

The result: the tumor repeated root has obvious tumor-inhibiting action according to tumor weight prompting medicine of the present invention that records and 5-FU group, sees Table 2.

Each experimental mice tumor-inhibiting action of table 2 is observed

Medicine group of the present invention and Chinese drug-treated group compare: P＜0.0.5

4. body weight

The result: 5-FU group mice body weight does not have significant difference before and after the medication, and prompting 5-FU has the effect that suppresses weight of mice.All the other respectively organize the mice body weight all increases more than the 4.26g, and there were significant differences before and after the medication sees Table 3.

Body weight change before and after each experimental mice experiment of table 3 (g, x ± SD)

The following example all can be realized the effect of above-mentioned experimental example.(dosage form of the part of summary of the invention should all embody in an embodiment)

Embodiment 1

Moschus 10g, Semen Momordicae (shell and deoil) 50g, Radix Aconiti Kusnezoffii Preparata 50g, Resina Liquidambaris 50g, Olibanum (system) 25g, Myrrha (processed) 25g, Oletum Trogopterori (vinegar stir-fry) 50g, Radix Angelicae Sinensis (wine stir-fry) 25g, Pheretima 50g, XIANGMO(sic) 4g

Embodiment 2

[method for making] above ten flavors, except that the artificial Moschus, nine flavors such as all the other Semen Momordicaes are ground into fine powder, with artificial Moschus's porphyrize, with above-mentioned powder facing-up, sieve; Get fine powder, add the edible vegetable oil that 0.5-1.5 doubly measures, grind, be pressed into 1000 of soft capsules, promptly get the soft capsule of compositions through conventional technology.

Embodiment 3

Moschus 10g, Semen Momordicae (shell and deoil) 50g, Radix Aconiti Kusnezoffii Preparata 50g, Herba Leonuri 50g, Olibanum (system) 25g, Herba Taraxaci 30g, Rhizoma Corydalis 50g, Radix Angelicae Sinensis (wine stir-fry) 25g, Pheretima 50g, XIANGMO(sic) 4g

4 compositions pills of embodiment discrimination method:

(1) it is an amount of to get embodiment 1 finished product, is ground into fine powder, takes by weighing 5g, the 20ml that adds diethyl ether, and supersound process 20 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (9:1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

(2) get Olibanum control medicinal material 0.1g, the 1ml that adds diethyl ether flooded 1 hour, and supernatant is medical material solution in contrast.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each the 5 μ l of need testing solution under control medicinal material solution and discriminating (2) item, put respectively on same silica gel g thin-layer plate, with petroleum ether (60-90 ℃) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.

(3) it is an amount of to get embodiment 1 finished product, is ground into fine powder, takes by weighing 4g, add 70% ethanol 50ml, placement is spent the night, and filters, filtrate is steamed to there not being the ethanol flavor, add water 20ml dissolving, with chloroform extraction twice, each 20ml, merge chloroform liquid, evaporate to dryness, residue is with methanol 2ml dissolving, as need testing solution.Other gets Pheretima control medicinal material 1g, shines medical material solution in pairs with legal system.According to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel H lamellae, with cyclohexane extraction-ethyl acetate (9:1) is developing solvent, launches twice, takes out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

5 compositions pills of embodiment inspection method:

It is an amount of that aconitine limit is got embodiment 1 finished product, is ground into fine powder, takes by weighing 10g, put in the conical flask, add ammonia solution 10ml, mix thoroughly, placed 2 hours, and added absolute ether 120ml, jolting 1 hour, placed 24 hours, filter, filtrate adds hydrochloric acid solution (4 → 100) jolting and extracts 3 (20ml, 15ml, 15ml), merge hydrochloric acid solution, hydrochloric acid solution adds strong ammonia solution, transfers Ph value to 9～10, adding the absolute ether jolting extracts 3 times, each 20ml merges ether solution, volatilizes, residue adds dehydrated alcohol 1ml makes dissolving, as need testing solution.Other gets the aconitine reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw need testing solution 15 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with benzene-ethyl acetate-diethylamine (7:2:0.5) is developing solvent, presaturation launched after 2 hours, take out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of appearance should or speckle not occur less than the speckle of reference substance.

Other is not except that dissolve scattered time limit is checked, other should meet every regulation relevant under the pill item (2005 editions one appendix I A of Chinese Pharmacopoeia).

6 compositions pills of embodiment content assaying method:

Measure according to gas chromatography (2005 editions one appendix VI E of Chinese Pharmacopoeia).

Chromatographic condition and system suitability test are immobile phase with silicone (OV-17), and coating concentration is 5%; 190 ℃ of column temperatures, 220 ℃ of injector temperatures, 240 ℃ of detector temperatures are carrier gas with nitrogen.Number of theoretical plate calculates by the muscone peak should be not less than 1500.It is an amount of that correction factor mensuration is got AI3-36122, and accurate the title decides, and adds cyclohexane extraction and makes the solution that every 1ml contains 0.2mg, as inner mark solution.It is an amount of that other gets the muscone reference substance, and accurate the title decides, and adds cyclohexane extraction and makes the solution that every 1ml contains 0.2mg, in contrast the product storing solution.Above two kinds of each 2ml of solution of accurate absorption put in the measuring bottle of same 10ml, add cyclohexane extraction and are diluted to scale, shake up, in contrast product solution.Draw reference substance solution 2 μ l, inject gas chromatograph, the calculation correction factor.

Assay method is got embodiment 1 finished product, is ground into fine powder, gets powder 1g, and accurate the title decides, mark liquid 2ml in accurate the adding, and cyclohexane extraction 8ml, close plug, jolting, ultrasonic 30min, filtration, the accurate subsequent filtrate 2 μ l that draw, inject gas chromatograph calculates, promptly.

The every 1g of embodiment 1 finished product contains the artificial Moschus with muscone (C ₁₆H ₃₀O) calculate, must not be less than 0.3mg.

7 compositions pills of embodiment method of quality control:

[discriminating]

(2) get Olibanum control medicinal material 0.1g, the 1ml that adds diethyl ether flooded 1 hour, and supernatant is medical material solution in contrast.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each the 5 μ l of need testing solution under control medicinal material solution and discriminating (1) item, put respectively on same silica gel g thin-layer plate, with petroleum ether (60-90 ℃) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.

It is an amount of that [inspection] aconitine limit is got embodiment 1 finished product, is ground into fine powder, takes by weighing 10g, put in the conical flask, add ammonia solution 10ml, mix thoroughly, placed 2 hours, and added absolute ether 120ml, jolting 1 hour, placed 24 hours, filter, filtrate adds hydrochloric acid solution (4 → 100) jolting and extracts 3 (20ml, 15ml, 15ml), merge hydrochloric acid solution, hydrochloric acid solution adds strong ammonia solution, transfers Ph value to 9～10, adding the absolute ether jolting extracts 3 times, each 20ml merges ether solution, volatilizes, residue adds dehydrated alcohol 1ml makes dissolving, as need testing solution.Other gets the aconitine reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw need testing solution 15 μ 1, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with benzene-ethyl acetate-diethylamine (7:2:0.5) is developing solvent, presaturation launched after 2 hours, take out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of appearance should or speckle not occur less than the speckle of reference substance.

[assay] measured according to gas chromatography (2005 editions one appendix VI E of Chinese Pharmacopoeia).

[function cures mainly] mass dissipating and swelling eliminating, blood-activating analgetic.Be used for scrofula, goiter, breast carcinoma, the nodules of the breast of mental disorder due to stagnating, disease is seen lump one place or number place under skin or the skin, pushes away actively, or bone and osteoarthritis, color of the leather is constant, swollen has a pain firmly.

It is oral that [usage and dosage] smashes the back, a 1.2～3g, and 2 times on the one, children's is cut down according to the circumstance.

[attention] anemia of pregnant woman forbidding.

The heavy 3g of [specification] per 100 balls.

[storage] sealing.

Claims

1, a kind of have a mass dissipating and swelling eliminating, and the Chinese medicine composition of effect of dissolving stasis and relieving pain is characterized in that said composition is to be made by the crude drug of following weight ratio:

2, Chinese medicine composition as claimed in claim 1 is characterized in that said composition can be made by the crude drug of following weight ratio:

3, Chinese medicine composition as claimed in claim 1 is characterized in that this Chinese medicine composition can be made by the crude drug of following weight ratio:

4, Chinese medicine composition as claimed in claim 3 is characterized in that this Chinese medicine composition can be made by the crude drug of following weight ratio:

5, Chinese medicine composition as claimed in claim 3 is characterized in that this Chinese medicine composition can be made by the crude drug of following weight ratio:

6,, it is characterized in that technology adding adjuvant is made clinical acceptable forms such as tablet, capsule, oral liquid, drop pill, spray, granule routinely as any described Chinese medicine composition of claim 1-5; Described adjuvant comprises solvent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent, lubricant, substrate etc.

7, Chinese medicine composition as claimed in claim 6 is characterized in that the preparation method of this Chinese medicine composition pill is:

More than ten flavors, except that the artificial Moschus, all the other Semen Momordicaes etc. nine flavor is ground into fine powder, with artificial Moschus's porphyrize, with above-mentioned powder facing-up, sieves.Every 100g powder adds starch 25g, mixing, and in addition with starch 5g system 14% starch slurry, general ball, dry below 80 ℃, promptly.

8,, it is characterized in that this method of quality control comprises one or more in following discrimination method and/or assay and/or the inspection as claim 1-5 any one or 7 described method of quality control:

Differentiate:

(1) it is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, take by weighing to be equivalent to crude drug 3-4g, and the 10-30ml that adds diethyl ether, supersound process 10-30 minute, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (7-9:1-3) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

(2) get Olibanum control medicinal material 0.1g, the 1ml that adds diethyl ether flooded 1-3 hour, and supernatant is medical material solution in contrast.Test according to thin layer chromatography (2005 editions appendix VIB of Chinese Pharmacopoeia), draw each the 5 μ l of need testing solution under control medicinal material solution and discriminating (1) item, put respectively on same silica gel g thin-layer plate, with petroleum ether (60-90 ℃)-ethyl acetate (90-100:0-10) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;

(3) it is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, takes by weighing to be equivalent to crude drug 3-4g, add the ethanol 40-60ml of 60-80%, placement is spent the night, and filters, filtrate is steamed to there not being the ethanol flavor, add water 10-30ml dissolving, use chloroform extraction 1-3 time, each 10-30ml, merge chloroform liquid, evaporate to dryness, residue is with methanol 2ml dissolving, as need testing solution.Other gets Pheretima control medicinal material 1g, shines medical material solution in pairs with legal system.According to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel H lamellae, with cyclohexane extraction-ethyl acetate (8-10:0-2) is developing solvent, launches twice, takes out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

Check:

It is an amount of that aconitine limit is got pharmaceutical composition of the present invention, is ground into fine powder, takes by weighing to be equivalent to crude drug 7-8g, put in the conical flask, add ammonia solution 10ml, mix thoroughly, placed 1-3 hour, and added absolute ether 100-150ml, jolting 0.5-2 hour, placed 12-36 hour, filter, filtrate adds hydrochloric acid solution (4 → 100) jolting and extracts 3 (15-25ml, 10-20ml, 10-20ml), merge hydrochloric acid solution, hydrochloric acid solution adds strong ammonia solution, transfers Ph value to 9～10, adding the absolute ether jolting extracts 3 times, each 15-25ml merges ether solution, volatilizes, residue adds dehydrated alcohol 1ml makes dissolving, as need testing solution.Other gets the aconitine reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw need testing solution 15 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with benzene-ethyl acetate-diethylamine (5-10:1-3:0.5-2) is developing solvent, presaturation launched after 2 hours, take out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of appearance should or speckle not occur less than the speckle of reference substance;

Assay:

Measure according to gas chromatography (2005 editions one appendix VI E of Chinese Pharmacopoeia);

Chromatographic condition and system suitability test are immobile phase with silicone (OV-17), and coating concentration is 5%; 190 ℃ of column temperatures, 220 ℃ of injector temperatures, 240 ℃ of detector temperatures are carrier gas with nitrogen.Number of theoretical plate calculates by the muscone peak should be not less than 1500.It is an amount of that correction factor mensuration is got AI3-36122, and accurate the title decides, and adds cyclohexane extraction and makes the solution that every 1ml contains 0.2mg, as inner mark solution.It is an amount of that other gets the muscone reference substance, and accurate the title decides, and adds cyclohexane extraction and makes the solution that every 1ml contains 0.2mg, in contrast the product storing solution.Above two kinds of each 2ml of solution of accurate absorption put in the measuring bottle of same 10ml, add cyclohexane extraction and are diluted to scale, shake up, in contrast product solution.Draw reference substance solution 2 μ l, inject gas chromatograph, the calculation correction factor;

Assay method is got pharmaceutical preparation of the present invention, is ground into fine powder, gets powder and is equivalent to crude drug 0.5-1.5g, and accurate the title decides, mark liquid 2ml in accurate the adding, cyclohexane extraction 8ml, close plug, jolting, ultrasonic 20-40min filters, the accurate subsequent filtrate 2 μ l that draw, inject gas chromatograph calculates, promptly;

9, as the method for quality control of Chinese medicine composition as described in the claim 8, it is characterized in that this method of quality control comprise following discrimination method and/or assay and/or check in one or more:

Differentiate:

(1) it is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, take by weighing to be equivalent to crude drug 3.85g, and the 20ml that adds diethyl ether, supersound process 20 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (9: 1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

(2) get Olibanum control medicinal material 0.1g, the 1ml that adds diethyl ether flooded 1 hour, and supernatant is medical material solution in contrast.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw each the 5 μ l of need testing solution under control medicinal material solution and discriminating (1) item, put respectively on same silica gel g thin-layer plate, with petroleum ether (60-90 ℃) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;

(3) it is an amount of to get pharmaceutical preparation of the present invention, is ground into fine powder, takes by weighing to be equivalent to crude drug 3.08g, add 70% ethanol 50ml, placement is spent the night, and filters, filtrate is steamed to there not being the ethanol flavor, add water 20ml dissolving, with chloroform extraction twice, each 20ml, merge chloroform liquid, evaporate to dryness, residue is with methanol 2ml dissolving, as need testing solution.Other gets Pheretima control medicinal material 1g, shines medical material solution in pairs with legal system.According to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel H lamellae, with cyclohexane extraction-ethyl acetate (9:1) is developing solvent, launches twice, takes out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

Check:

It is an amount of that aconitine limit is got pharmaceutical composition of the present invention, is ground into fine powder, takes by weighing to be equivalent to crude drug 7.7g, put in the conical flask, add ammonia solution 10ml, mix thoroughly, placed 2 hours, and added absolute ether 120ml, jolting 1 hour, placed 24 hours, filter, filtrate adds hydrochloric acid solution (4 → 100) jolting and extracts 3 (20ml, 15ml, 15ml), merge hydrochloric acid solution, hydrochloric acid solution adds strong ammonia solution, transfers Ph value to 9～10, adding the absolute ether jolting extracts 3 times, each 20ml merges ether solution, volatilizes, residue adds dehydrated alcohol 1ml makes dissolving, as need testing solution.Other gets the aconitine reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (2005 editions one appendix VI B of Chinese Pharmacopoeia), draw need testing solution 15 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with benzene-ethyl acetate-diethylamine (7:2:0.5) is developing solvent, presaturation launched after 2 hours, take out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of appearance should or speckle not occur less than the speckle of reference substance;

Other is not except that dissolve scattered time limit is checked, other should meet every regulation relevant under the pill item (2005 editions one appendix I A of Chinese Pharmacopoeia);

Assay:

Get pharmaceutical preparation of the present invention, be ground into fine powder, get powder and be equivalent to crude drug 0.77g, the accurate title, decide, mark liquid 2ml in accurate the adding, and cyclohexane extraction 8ml, close plug, jolting, ultrasonic 30min, filtration, the accurate subsequent filtrate 2 μ l that draw, inject gas chromatograph calculates, promptly;