CN1895605A - Tangerine-seed phlegm and cough preparation, its making method and quality control - Google Patents

Abstract

A Chinese medicine in the form syrup or oral liquid for treating cough and resolving phlegm is prepared from 8 Chinese-medicinal materials including pummelo peel, stemona root, tuckahoe, liquorice root, etc. Its preparing process and quality control method are also disclosed.

Description

'Juhong Tanke ' and preparation method and method of quality control

Technical field: the present invention relates to a kind of 'Juhong Tanke ' and preparation method thereof and method of quality control, belong to technical field of Chinese medicines.

Background technology: 'Juhong Tanke ' is made up of Exocarpium Citri Grandis, the Radix Stemonae, Semen Armeniacae Amarum, Fructus Schisandrae Chinensis, Rhizoma pinelliae cordatae, Poria, Rhizoma Cynanchi Stauntonii, Radix Glycyrrhizae eight flavor medical materials, having regulates the flow of vital energy eliminates the phlegm, the effect of nourishing the lung to arrest cough, be used for the treatment of flu, the abundant expectoration cough that bronchitis, pharyngolaryngitis cause, diseases such as asthma, its clinical application effect is remarkable.Defectives such as existing 'Juhong Tanke ' mainly contains soft extract, granule and oral liquid, and it is relatively poor that these preparations exist mouthfeel, and being suitable for crowd's scope has certain limitation, and quality is stable inadequately.And the quality control standard of existing 'Juhong Tanke ' is simple, and product quality can not be controlled fully and effectively, thereby has influenced its clinical efficacy.

Summary of the invention:

The objective of the invention is to: a kind of 'Juhong Tanke ' and preparation method and method of quality control are provided, the present invention is directed to the deficiencies in the prior art, syrup that is provided and oral liquid mouthfeel are good, easy for patients to accept, taking convenience, accurate, end product quality is stable, has enlarged suitable crowd's scope; And studied and defined more effective method of quality control, improved the quality control standard of 'Juhong Tanke ', thereby guaranteed its clinical efficacy.

The present invention constitutes like this: according to part by weight, it is to be prepared from Exocarpium Citri Grandis 250-350, processed with honey Radix Stemonae 10-50, Semen Armeniacae Amarum 60-150, Fructus Schisandrae Chinensis 10-50, controlling the water circulation Rhizoma Pinelliae 10-50, Poria 10-50, Rhizoma Cynanchi Stauntonii 30-80, Radix Glycyrrhizae 5-30 and adjuvant; Wherein the used adjuvant of syrup is: 10-80% sucrose, 0.1-0.3% sodium benzoate, 0.01-0.1% ethyl hydroxybenzoate, 1-5% propylene glycol; The used adjuvant of oral liquid is: 10-50% simple syrup and 0.1-0.3% sodium benzoate, 0.01-0.1% ethyl hydroxybenzoate.

The preparation method of Juhong Tanke syrup of the present invention is: Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation, collect Aromatic water, and the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, Radix Glycyrrhizae Six-element, adding 5-20 times of water gaging decocts 1-5 time, each 0.5-5 hour, filter, filtrate and above-mentioned aqueous solution merge, and concentrate, add ethanol, make to contain alcohol amount and reach 40～90%, left standstill 8-50 hour, get supernatant and reclaim ethanol, concentrate, add sucrose, 0.1-0.3% sodium benzoate and the 0.01-0.1% ethyl hydroxybenzoate of preparation total amount 10-80%, heating for dissolving is put cold, add above-mentioned Aromatic water and 1-5% propylene glycol, mixing adds water to 1000ml, promptly.

The preparation method of red tangerine peel oral liquor for treating productive cough of the present invention is: Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation, collect Aromatic water, and the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, the Radix Glycyrrhizae Six-element adds 5-20 times of water gaging and decocts 1-5 time, each 0.5-5 hour, filter, filtrate and above-mentioned aqueous solution merge, and concentrate, add ethanol, make to contain alcohol amount and reach 40～90%, left standstill 8-50 hour, get supernatant and reclaim ethanol, concentrate, add water to the 40-100% of total amount, 4 ℃～8 ℃ cold preservation 30-100h filter, filtrate adds simple syrup to sugar content 10-50%, add the 0.1-0.3% sodium benzoate, the 0.01-0.1% ethyl hydroxybenzoate boils dissolving, adds water to 1000ml, stir evenly, filter, embedding, promptly.

The present invention also provides the method for quality control of Juhong Tanke syrup and oral liquid in addition.

Method of quality control of the present invention mainly comprise in character, discriminating, inspection and the assay project partly or entirely; Wherein differentiate the thin layer chromatography discriminating that comprises Exocarpium Citri Grandis, Radix Glycyrrhizae and Poria in the preparation; Assay is that the contained naringin of Exocarpium Citri Grandis in the preparation is carried out assay.

The discrimination method of Exocarpium Citri Grandis is to be contrast with the Exocarpium Citri Grandis control medicinal material, and with toluene: ethyl acetate: formic acid: water=1-10: 1-10: 0.1-5: 0.1-5 is the thin layer chromatography of developing solvent; The discrimination method of Radix Glycyrrhizae is to be contrast with the enoxolone reference substance, and with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-20: 10-30: 1-15: 0.1-5 is the thin layer chromatography of developing solvent; The discrimination method of Poria is to be contrast with the Poria control medicinal material, is the thin layer chromatography of developing solvent with toluene: ethyl acetate=1-20: 0.5-10.

Concrete discrimination method comprises the part or all of of following project:

(1) get this preparation 1-10ml, add ethyl acetate 5-50ml jolting and extract, divide and get ethyl acetate liquid, evaporate to dryness, residue add dehydrated alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets Exocarpium Citri Grandis control medicinal material 0.1-1 gram, adds methanol 5-50ml, puts in the water-bath reflux 10-100 minute, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 0.5-3ml makes dissolving, in contrast medical material solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 1-10 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate: formic acid: water=1-10: 1-10: 0.1-5: 0.1-5 is developing solvent, launch, take out, dry, spray is put under the ultra-violet lamp 365nm and is inspected with 3% aluminum chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

(2) get this preparation 10-100ml, extraction 1-8 time that adds diethyl ether discards ether layer, water layer is got n-butanol layer, evaporate to dryness with water saturated n-butanol extraction 1-5 time, add the 1-10ml concentrated hydrochloric acid, 10-100ml chloroform, reflux 0.5-5 hour, put cold, wash with water 1-5 time, abandon water layer, get the chloroform layer evaporate to dryness, residue 0.2-2ml anhydrous alcohol solution is as need testing solution; Extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution in addition; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 2-20 μ l of above-mentioned solution, put in same silica gel G F respectively ₂₅₄On the lamellae, with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-20: 10-30: 1-15: 0.1-5 is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp 254nm and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

(3) get this preparation 10-100ml, use chloroform extraction 1-6 time, chloroform solution is concentrated into 0.5-5ml, makes need testing solution; Other gets Poria control medicinal material 0.5-3g, adds methanol 10-50ml, and reflux 10-100 minute, filter, filtrate water bath method, residue add water 1-20ml dissolving, use chloroform extraction 1-6 time, get chloroform solution and are concentrated into 0.5-3ml, in contrast medical material liquid; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 5-20 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, be developing solvent with toluene: ethyl acetate=1-20: 0.5-10, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material chromatograph relevant position on, the fluorescence speckle of same color is arranged.

The content assaying method of naringin is to be contrast with the naringin reference substance in the Exocarpium Citri Grandis, and with methanol or acetonitrile: acetic acid: water=20-50: 1-10: 50-80 is the high performance liquid chromatography of mobile phase.

Concrete content assaying method is:

According to the Chinese Pharmacopoeia high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol or acetonitrile: acetic acid: water=20-50: 1-10: 50-80; The detection wavelength is 283nm; Theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of reference substance solution: the naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.01-0.5mg, promptly;

The preparation of need testing solution: precision is measured this preparation 1-10ml, puts in the 10-100ml volumetric flask, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate, promptly;

Algoscopy: accurate respectively reference substance solution and each 5-20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly;

The every 1ml of syrup contains Exocarpium Citri Grandis with naringin C in this preparation ₂₇H ₃₂O ₁₄Meter must not be less than 0.6mg; The every 1ml of oral liquid contains Exocarpium Citri Grandis with naringin C ₂₇H ₃₂O ₁₄Meter must not be less than 0.3mg.

Described method of quality control comprises:

Character:

For syrup: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

For oral liquid: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

Differentiate: (1) gets this preparation 1-10ml, adds ethyl acetate 5-50ml jolting and extracts, and divides and gets ethyl acetate liquid, and evaporate to dryness, residue add dehydrated alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets Exocarpium Citri Grandis control medicinal material 0.1-1 gram, adds methanol 5-50ml, puts in the water-bath reflux 10-100 minute, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 0.5-3ml makes dissolving, in contrast medical material solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 1-10 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate: formic acid: water=1-10: 1-10: 0.1-5: 0.1-5 is developing solvent, launch, take out, dry, spray is put under the ultra-violet lamp 365nm and is inspected with 3% aluminum chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

(2) get this preparation 10-100ml, extraction 1-8 time that adds diethyl ether discards ether layer, water layer is got n-butanol layer, evaporate to dryness with water saturated n-butanol extraction 1-5 time, add the 1-10ml concentrated hydrochloric acid, 10-100ml chloroform, reflux 0.5-5 hour, put cold, wash with water 1-5 time, abandon water layer, get the chloroform layer evaporate to dryness, residue 0.2-2ml anhydrous alcohol solution is as need testing solution; Extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution in addition; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 2-20 μ l of above-mentioned solution, put in same silica gel G F respectively ₂₅₄On the lamellae, with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-20: 10-30: 1-15: 0.1-5 is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp 254nm and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

(3) get this preparation 10-100ml, use chloroform extraction 1-6 time, chloroform solution is concentrated into 0.5-5ml, makes need testing solution; Other gets Poria control medicinal material 0.5-3g, adds methanol 10-50ml, and reflux 10-100 minute, filter, filtrate water bath method, residue add water 1-20ml dissolving, use chloroform extraction 1-6 time, get chloroform solution and are concentrated into 0.5-3ml, in contrast medical material liquid; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 5-20 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, be developing solvent with toluene: ethyl acetate=1-20: 0.5-10, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material chromatograph relevant position on, the fluorescence speckle of same color is arranged;

Check:

Relative density: get syrup,, should be not less than 1.10 according to Chinese Pharmacopoeia relative density inspection technique;

PH value: get syrup or oral liquid,, should be 3.0～7.0 according to Chinese Pharmacopoeia pH value inspection technique;

Other: should meet every regulation relevant under Chinese Pharmacopoeia syrup or the mixture item;

Assay: shine the Chinese Pharmacopoeia high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol or acetonitrile: acetic acid: water=20-50: 1-10: 50-80; The detection wavelength is 283nm; Theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of reference substance solution: the naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.01-0.5mg, promptly;

The preparation of need testing solution: precision is measured this preparation 1-10ml, puts in the 10-100ml volumetric flask, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate, promptly;

Algoscopy: accurate respectively reference substance solution and each 5-20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly;

The every 1ml of syrup contains Exocarpium Citri Grandis with naringin C in this preparation ₂₇H ₃₂O ₁₄Meter must not be less than 0.6mg; The every 1ml of oral liquid contains Exocarpium Citri Grandis with naringin C ₂₇H ₃₂O ₁₄Meter must not be less than 0.3mg.

The applicant has carried out a series of experimental study to the preparation technology and the method for quality control of preparation of the present invention, to guarantee its science, reasonable, feasible, effective.

One, adjuvant is selected

1, cosolvent is selected: because of the said preparation syrup when the preparation, add tangerine and Semen Armeniacae Amarum distillate, solution can be muddy, put the meeting layering for a long time, need to add a certain amount of cosolvent, just can make solution homogeneous, stable, we have selected glycerol respectively, propylene glycol, tween 80 finds that the solution of adding propylene glycol is more stable.

2, choice of preservatives: syrup and oral liquid are as liquid preparation for oral administration, though in process for preparation, noted the preparation environment, apparatus, the cleaning sterilizing of container, guaranteed that preparation meets the regulation of health examination before enabling, but the patient is in the process of taking, because repeatedly unpacking, still easily by microbial contamination, so also need add suitable antiseptic in the preparation, sodium benzoate bacteriostasis in acid solution is stronger, along with pH rising bacteriostasis weakens gradually, p-Hydroxybenzoate all has good fungistatic effect in pH value 4～8 scopes, but its dissolubility in water is relatively poor, add compound preservative sodium benzoate and ethyl hydroxybenzoate so we adopt, the best is: 0.2% sodium benzoate and 0.05% ethyl hydroxybenzoate.

Two, quality standard research

(1) method for measuring naringin content research

Preparation of the present invention is to be made up of eight flavor medical materials such as Exocarpium Citri Grandis, the Radix Stemonae (processed with honey), Semen Armeniacae Amarum, Poria, Rhizoma pinelliae cordatae (system), Fructus Schisandrae Chinensis, Rhizoma Cynanchi Stauntonii, Radix Glycyrrhizae, from prescription, principal agent is an Exocarpium Citri Grandis in the side, so the contained naringin of principal agent composition Exocarpium Citri Grandis medical material in the preparation is carried out assay, and methodology is studied.

1, precision test: accurate naringin reference substance solution (0.058mg/ml) the 10 μ l that draw, inject chromatograph of liquid, measure peak area, repeat sample introduction 5 times, average peak area is 1261338, RSD is 1.07%.Show that precision is good.

The test of naringin reference substance solution precision

The sample introduction number of times	1	2	3	4	5	Meansigma methods	RSD(％)
								Peak area	1273186	1268215	1271424	1250555	1243309	1261338	1.07

2, replica test: get this preparation, the preparation method by test liquid under the assay item among the present invention prepares 5 parts of test liquids respectively, and sample introduction is measured peak area, and the naringin average content is 1.4095mg/ml, and RSD is 2.21%.Show that repeatability is good.

The replica test of naringin in the preparation test sample

The sample introduction number of times	1	2	3	4	5	Meansigma methods	RSD(％)
								Content (mg/ml)	1.4478	1.3974	1.4095	1.4275	1.3654	1.4095	2.21

3, stability test: get this preparation, prepare test liquid by the preparation method of test liquid under the assay item among the present invention, measure its naringin peak area respectively at 0,2,4,6,8 hour, average peak area is 1210903.8, and RSD is 1.14%.Show that naringin is stable in 8 hours in the need testing solution.

The stability test of naringin in the preparation test sample

Time (h)

0

2

4

6

8

Meansigma methods

RSD(％)

Peak area

1224953

1210173

1197829

1224713

1196851

1210903.8

1.14

4, recovery test: adopt the application of sample absorption method, precision is got each 1ml of this preparation (average content is 1.4095mg/ml) respectively, put in the 50ml measuring bottle, (with methanol is solvent to accurate adding naringin reference substance, make that to contain naringin be 0.2670mg/ml) solution 5ml, add methanol to scale, shake up, filter membrane (0.45 μ m) filters, and makes test liquid.The accurate respectively 10 μ l of absorption inject chromatograph of liquid, and the record chromatograph is measured content, calculate recovery rate.Average recovery rate is 99.11%, and RSD is 2.55%, proves that this method is feasible.

Naringin is measured recovery test in the need testing solution

Experiment number	Sample size (ml)	Contain naringin (mg)	Add naringin (mg)	The amount of recording (mg)	The response rate (%)	Average recovery rate (%)	RSD (％)
								1	1.0	1.4095	1.3350	2.7356	99.34	99.11	2.55
2	1.0	1.4095	2.7005	96.70
					3	1.0	1.4095	2.6960	96.37
4	1.0	1.4095	2.7663	101.64
					5	1.0	1.4095	2.7648	101.52

(2) Exocarpium Citri Grandis thin layer chromatography research

With Exocarpium Citri Grandis in the Exocarpium Citri Grandis control medicinal material discriminating side.

The reference substance solution preparation method: get Exocarpium Citri Grandis control medicinal material 0.3 gram, add methanol 10ml, put in the water-bath reflux 20 minutes, filter, filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, in contrast medical material solution.

Need testing solution preparation method one: the thing 5ml that gets it filled, add ethyl acetate 10ml jolting and extract, divide and get acetic acid ethyl fluid, evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution.Other gets and lacks the negative test sample 5ml of Exocarpium Citri Grandis, gets negative need testing solution with legal system.

Need testing solution preparation method two: the thing 5ml that gets it filled, the 10ml jolting that adds diethyl ether is extracted, and divides and gets ether solution, and evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution.Other gets and lacks the negative test sample 5ml of Exocarpium Citri Grandis, gets negative need testing solution with legal system.

Developing solvent is selected: with the mixed solution of toluene, ethyl acetate, formic acid, water different proportion, the mixed solution of ethyl acetate, butanone, formic acid, water different proportion is developing solvent.

The result: according to the need testing solution of method one preparation, with toluene: ethyl acetate: formic acid: water=1-10: 1-10: 0.1-5: 0.1-5 is developing solvent, launches, and takes out, and dries, and spray is put under the ultra-violet lamp 365nm and inspected with 3% aluminum chloride alcoholic solution.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.Through repeatedly experiment, this law separator well, clear spot, negative noiseless, favorable reproducibility.Best developing solvent is a toluene: ethyl acetate: formic acid: water=2: 3: 0.3: 0.3.

(3) thin layer chromatography of Radix Glycyrrhizae research

With licorice medicinal materials in enoxolone reference substance or the Radix Glycyrrhizae control medicinal material discriminating side.

Reference substance solution preparation method one: extracting liquorice control medicinal material 0.5g, same method adds methanol 2ml dissolving, makes Radix Glycyrrhizae control medicinal material solution.

Reference substance solution preparation method two: extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 1mg, in contrast product solution.

Need testing solution preparation method one: the thing 10ml that gets it filled, the 40ml that adds diethyl ether, reflux 1 hour, filter, medicinal residues add methanol 30ml, reflux 1h, filter, filtrate evaporate to dryness, residue add water 40ml makes dissolving, with n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, wash with water 3 times, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.The negative test sample 10ml of extracting liquorice makes the negative need testing solution of scarce Radix Glycyrrhizae with method in addition.

Need testing solution preparation method two: the thing 30ml that gets it filled, the extraction 4 times that adds diethyl ether, each 20ml, abandon ether layer, water layer is with water saturated n-butanol extraction 3 times, each 20ml, get n-butanol layer, evaporate to dryness adds the 5ml concentrated hydrochloric acid, the 50ml chloroform, reflux 1 hour is put cold, wash with water 3 times, each 30ml abandons water layer, get the chloroform layer evaporate to dryness, residue is with about 0.5ml anhydrous alcohol solution, as need testing solution.The negative control 30ml of extracting liquorice gets the Radix Glycyrrhizae negative control solution with legal system in addition.

Above reference substance and test sample are put respectively in the silica gel g thin-layer plate or the same silica gel G F of same usefulness 1% sodium hydroxide solution preparation ₂₅₄On the lamellae.

Developing solvent is selected: with the mixed solution of ethyl acetate, formic acid, glacial acetic acid, water different proportion; Mixed solution with petroleum ether, benzene, ethyl acetate, glacial acetic acid different proportion is developing solvent; Mixed solution with petroleum ether, benzene, acetone different proportion is developing solvent, launches, and takes out, and dries, and spray is with 10% ethanol solution of sulfuric acid or do not spray.

Result: prepare respectively according to need testing solution preparation method two and reference substance solution preparation method two, draw each 4 μ l of above-mentioned solution, put in same silica gel G F respectively ₂₅₄On the lamellae, with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-20: 10-30: 1-15: 0.1-5 is developing solvent, launches, take out, dry, put under the ultra-violet lamp (254nm) and inspect, in the test sample chromatograph, with the corresponding position of reference substance on, show same color fluorescence speckle, prove that through test of many times this method separating degree is good, the speckle colour developing is clear, negative noiseless, the method favorable reproducibility.Best developing solvent is 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=10: 20: 7: 0.5.

(4) thin layer chromatography of Poria research

With Poria medical material in the Poria control medicinal material discriminating side.

The reference substance solution preparation method: get control medicinal material 1g and add methanol 20ml, backflow 30min filters, and filtrate water bath method, residue add water 5ml, use equal-volume chloroform extraction three times, get chloroform solution and are concentrated into about 1ml medical material liquid in contrast.

Need testing solution preparation method one: the thing 20ml that gets it filled, use chloroform extraction three times, each 15ml concentrates chloroform solution to 1ml, makes need testing solution.Get scarce Poria contrast 20ml, get negative control solution with legal system.

Need testing solution preparation method two: the thing 20ml that gets it filled, use extracted with diethyl ether three times, each 15ml concentrates ether to 1ml, makes need testing solution.Get scarce Poria contrast 20ml, get negative control solution with legal system.

Developing solvent is selected: respectively with the mixed solution of toluene-ethyl acetate different proportion; Mixed solution with toluene-ethyl acetate, water different proportion is developing solvent.

Result: according to the need testing solution of method one preparation, launch with toluene: ethyl acetate=1-20: 0.5-10, take out, airing is put under the ultra-violet lamp (365nm) and is inspected, in the test sample chromatograph, with the fluorescence speckle that same color is arranged on the control medicinal material relevant position, this method speckle colour developing is clear, negative noiseless, the method favorable reproducibility.Best developing solvent is a toluene: ethyl acetate=8: 3.

Compared with prior art, syrup provided by the present invention and oral liquid mouthfeel are good, are beneficial to and take, and be easy for patients to accept; Add suitable antiseptic and sucrose in the finished product,, pack steady quality through sterilization treatment; The method of quality control precision height of being formulated, favorable reproducibility, response rate height has improved the quality control standard of 'Juhong Tanke ', can control the quality of said preparation fully and effectively.

Further specify the present invention by the following examples, but not as limitation of the present invention.

Embodiments of the invention 1: Exocarpium Citri Grandis 300g, processed with honey Radix Stemonae 30g, Semen Armeniacae Amarum 100g, Fructus Schisandrae Chinensis 20g, controlling the water circulation Rhizoma Pinelliae 30g, Poria 30g, Rhizoma Cynanchi Stauntonii 50g, Radix Glycyrrhizae 10g

Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation are collected the 100ml Aromatic water, and the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, the Radix Glycyrrhizae Six-element, adding 10 times of water gagings decocts 2 times, each 2 hours, filter, filtrate and above-mentioned aqueous solution merge, and being concentrated into relative density is 1.02-1.35 (80 ℃), add ethanol, make to contain alcohol amount and reach 75～80%, left standstill 24 hours, get supernatant and reclaim ethanol, being concentrated into relative density is the clear paste of 1.18-1.20 (80 ℃), add 600g sucrose, 0.2% sodium benzoate and 0.05% ethyl hydroxybenzoate, heating for dissolving is put cold, add above-mentioned Aromatic water and 2% propylene glycol, mixing adds water to 1000ml, promptly gets syrup.

Embodiments of the invention 2: Exocarpium Citri Grandis 350g, processed with honey Radix Stemonae 50g, Semen Armeniacae Amarum 150g, Fructus Schisandrae Chinensis 50g, controlling the water circulation Rhizoma Pinelliae 50g, Poria 50g, Rhizoma Cynanchi Stauntonii 80g, Radix Glycyrrhizae 30g

Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation are collected the 200ml Aromatic water, and the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, Radix Glycyrrhizae Six-element add 20 times of water gagings and decoct each 0.5 hour 5 times, filter, filtrate and above-mentioned aqueous solution merge, and concentrate, add ethanol, make to contain the alcohol amount and reach 90%, left standstill 8 hours, get supernatant and reclaim ethanol, concentrate, add sucrose, 0.3% sodium benzoate and 0.1% ethyl hydroxybenzoate of 800g, heating for dissolving is put coldly, adds above-mentioned Aromatic water and 5% propylene glycol, mixing adds water to 1000ml, promptly gets syrup.

Embodiments of the invention 3: Exocarpium Citri Grandis 250g, processed with honey Radix Stemonae 10g, Semen Armeniacae Amarum 60g, Fructus Schisandrae Chinensis 10g, controlling the water circulation Rhizoma Pinelliae 10g, Poria 10g, Rhizoma Cynanchi Stauntonii 30g, Radix Glycyrrhizae 5g

Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation are collected the 50ml Aromatic water, and the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, Radix Glycyrrhizae Six-element add 5 times of water gagings and decoct each 5 hours 1 time, filter, filtrate and above-mentioned aqueous solution merge, and concentrate, add ethanol, make to contain the alcohol amount and reach 40%, left standstill 50 hours, get supernatant and reclaim ethanol, concentrate, add sucrose, 0.1% sodium benzoate and 0.01% ethyl hydroxybenzoate of 100g, heating for dissolving is put coldly, adds above-mentioned Aromatic water and 1% propylene glycol, mixing adds water to 1000ml, promptly gets syrup.

Embodiments of the invention 4: Exocarpium Citri Grandis 300g, processed with honey Radix Stemonae 30g, Semen Armeniacae Amarum 100g, Fructus Schisandrae Chinensis 20g, controlling the water circulation Rhizoma Pinelliae 30g, Poria 30g, Rhizoma Cynanchi Stauntonii 50g, Radix Glycyrrhizae 10g

Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation are collected the 100ml Aromatic water, and the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, the Radix Glycyrrhizae Six-element adds 10 times of water gagings and decocts each 2 hours 2 times, filter, filtrate and above-mentioned aqueous solution merge, and being concentrated into relative density is 1.02-1.35 (80 ℃), add ethanol, make to contain alcohol amount and reach 75～80%, left standstill 24 hours, get supernatant and reclaim ethanol, concentrate, add water to 800ml, 4 ℃～8 ℃ cold preservation 48h filter, filtrate adds simple syrup to sugar content 30%, add 0.2% sodium benzoate and 0.05% ethyl hydroxybenzoate, boil dissolving, add water to 1000ml, stir evenly, filter, embedding promptly gets oral liquid.

Embodiments of the invention 5: Exocarpium Citri Grandis 250g, processed with honey Radix Stemonae 50g, Semen Armeniacae Amarum 60g, Fructus Schisandrae Chinensis 10g, controlling the water circulation Rhizoma Pinelliae 50g, Poria 50g, Rhizoma Cynanchi Stauntonii 80g, Radix Glycyrrhizae 30g

Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation are collected the 150ml Aromatic water, and the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, Radix Glycyrrhizae Six-element add 20 times of water gagings and decoct each 0.5 hour 5 times, filter, filtrate and above-mentioned aqueous solution merge, and concentrate, add ethanol, make to contain alcohol amount and reach 90%, left standstill 8 hours, get supernatant and reclaim ethanol, concentrate, add water to 1000ml, 4 ℃～8 ℃ cold preservation 30h filter, filtrate adds simple syrup to sugar content 10%, add 0.3% sodium benzoate and 0.01% ethyl hydroxybenzoate, boil dissolving, add water to 1000ml, stir evenly, filter, embedding promptly gets oral liquid.

Embodiments of the invention 6: Exocarpium Citri Grandis 250g, processed with honey Radix Stemonae 10g, Semen Armeniacae Amarum 150g, Fructus Schisandrae Chinensis 50g, controlling the water circulation Rhizoma Pinelliae 10g, Poria 10g, Rhizoma Cynanchi Stauntonii 30g, Radix Glycyrrhizae 5g

Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation are collected the 80ml Aromatic water, and the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, Radix Glycyrrhizae Six-element add 5 times of water gagings and decoct each 5 hours 1 time, filter, filtrate and above-mentioned aqueous solution merge, and concentrate, add ethanol, make to contain alcohol amount and reach 40%, left standstill 50 hours, get supernatant and reclaim ethanol, concentrate, add water to the 400ml of total amount, 4 ℃～8 ℃ cold preservation 100h filter, filtrate adds simple syrup to sugar content 50%, add 0.1% sodium benzoate and 0.1% ethyl hydroxybenzoate, boil dissolving, add water to 1000ml, stir evenly, filter, embedding promptly gets oral liquid.

Embodiments of the invention 7: described syrup method of quality control is:

Character: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

Differentiate: (1) gets this preparation 5ml, adds ethyl acetate 10ml jolting and extracts, and divides and gets ethyl acetate liquid, and evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets Exocarpium Citri Grandis control medicinal material 0.3 gram, adds methanol 10ml, puts in the water-bath reflux 20 minutes, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, in contrast medical material solution; According to the Chinese Pharmacopoeia thin layer chromatography; Test, draw each 2 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate: formic acid: water=2: 3: 0.3: 0.3 is developing solvent, launch, take out, dry, spray is with 3% aluminum chloride alcoholic solution, 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 this preparation 30ml, the extraction 4 times that adds diethyl ether, each 20ml, abandon ether layer, water layer is with water saturated n-butanol extraction 3 times, each 20ml, get n-butanol layer, evaporate to dryness adds the 5ml concentrated hydrochloric acid, the 50ml chloroform, reflux 2 hours is put cold, wash with water 3 times, each 20ml abandons water layer, get the chloroform layer evaporate to dryness, residue is with about 0.5ml anhydrous alcohol solution, as need testing solution; Extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 1mg, in contrast product solution in addition; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 4 μ l of above-mentioned solution, put in same silica gel G F respectively ₂₅₄On the lamellae, with petroleum ether (60～90 ℃): benzene: ethyl acetate: glacial acetic acid=10: 20: 7: 0.5 is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp 254nm and inspects.In the test sample chromatograph, with the corresponding position of reference substance on, show the fluorescence speckle of same color.

(3) get this preparation 20ml, use chloroform extraction three times, each 15ml, chloroform solution is concentrated into 1ml, makes need testing solution; Other gets Poria control medicinal material 1g, adds methanol 20ml, and reflux 30 minutes filters, and filtrate water bath method, residue add water 5ml dissolving, use chloroform extraction three times, and each 10ml gets chloroform solution and is concentrated into about 1ml medical material liquid in contrast; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 10 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate=8: 3 is developing solvent, launches, take out, dry, put under the ultra-violet lamp 365nm and inspect, in the test sample chromatograph, with the control medicinal material relevant position on, the fluorescence speckle of same color is arranged.

Check:

Relative density: get syrup,, should be not less than 1.10 according to Chinese Pharmacopoeia relative density inspection technique;

PH value: get syrup,, should be 4.0～6.0 according to Chinese Pharmacopoeia pH value inspection technique;

Other: should meet every regulation relevant under the Chinese Pharmacopoeia syrup item;

Assay: shine the Chinese Pharmacopoeia high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol: acetic acid: water=35: 4: 65 is mobile phase; The detection wavelength is 283nm, and theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of reference substance solution: the naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.06mg, promptly;

The preparation of need testing solution: precision is measured this preparation 2ml, puts in the 50ml volumetric flask, and methanol shakes up to scale, filters with microporous filter membrane 0.45 μ m, gets subsequent filtrate, promptly;

Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.

The every 1ml of this syrup contains Exocarpium Citri Grandis with naringin C ₂₇H ₃₂O ₁₄Meter must not be less than 1.0mg.

Embodiments of the invention 8: described oral liquid method of quality control is:

Character: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

Differentiate: (1) gets this preparation 10ml, adds ethyl acetate 50ml jolting and extracts, and divides and gets ethyl acetate liquid, and evaporate to dryness, residue add dehydrated alcohol 3ml makes dissolving, as need testing solution; Other gets Exocarpium Citri Grandis control medicinal material 1 gram, adds methanol 50ml, puts in the water-bath reflux 100 minutes, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 3ml makes dissolving, in contrast medical material solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 10 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate: formic acid: water=10: 1: 0.1: 5 is developing solvent, launch, take out, dry, spray is put under the ultra-violet lamp 365nm and is inspected with 3% aluminum chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

(2) get this preparation 100ml, the extraction 8 times that adds diethyl ether discards ether layer, water layer is got n-butanol layer, evaporate to dryness with water saturated n-butanol extraction 5 times, add the 10ml concentrated hydrochloric acid, 100ml chloroform, reflux 5 hours, put cold, wash with water 5 times, abandon water layer, get the chloroform layer evaporate to dryness, residue 2ml anhydrous alcohol solution is as need testing solution; Extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 3mg, in contrast product solution in addition; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 2 μ l of above-mentioned solution, put in same silica gel G F respectively ₂₅₄On the lamellae, with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=20: 10: 1: 0.1 is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp 254nm and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.

(3) get this preparation 100ml, use chloroform extraction 6 times, chloroform solution is concentrated into 5ml, makes need testing solution; Other gets Poria control medicinal material 3g, adds methanol 50ml, and reflux 100 minutes filters, and filtrate water bath method, residue add water 20ml dissolving, use chloroform extraction 6 times, get chloroform solution and are concentrated into 3ml, in contrast medical material liquid; According to Chinese Pharmacopoeia thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate=20: 0.5 be developing solvent, launches, and taking-up is dried, and puts under the 365nm ultra-violet lamp and inspects; In the test sample chromatograph, with control medicinal material chromatograph relevant position on, the fluorescence speckle of same color is arranged.

Check:

PH value: get oral liquid,, should be 4.0～6.0 according to Chinese Pharmacopoeia pH value inspection technique;

Other: should meet every regulation relevant under the Chinese Pharmacopoeia mixture item;

Assay: shine the Chinese Pharmacopoeia high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Acetonitrile: acetic acid: water=20: 10: 80; The detection wavelength is 283nm; Theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of reference substance solution: the naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.5mg, promptly;

The preparation of need testing solution: precision is measured this preparation 10ml, puts in the 100ml volumetric flask, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate, promptly;

Algoscopy: accurate respectively reference substance solution and each 5 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.The every 1ml of this oral liquid contains Exocarpium Citri Grandis with naringin C ₂₇H ₃₂O ₁₄Meter must not be less than 0.3mg.

Embodiments of the invention 9: described syrup method of quality control is:

Character: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

Differentiate: (1) gets this preparation 1ml, adds ethyl acetate 5ml jolting and extracts, and divides and gets ethyl acetate liquid, and evaporate to dryness, residue add dehydrated alcohol 0.5ml makes dissolving, as need testing solution; Other gets Exocarpium Citri Grandis control medicinal material 0.1 gram, adds methanol 5ml, puts in the water-bath reflux 10 minutes, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 0.5ml makes dissolving, in contrast medical material solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 1 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate: formic acid: water=1: 10: 5: 0.1-5 is developing solvent, launch, take out, dry, spray is put under the ultra-violet lamp 365nm and is inspected with 3% aluminum chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

(2) get this preparation 10ml, the extraction 1 time that adds diethyl ether discards ether layer, water layer is got n-butanol layer, evaporate to dryness with water saturated n-butanol extraction 1 time, add the 1ml concentrated hydrochloric acid, 10ml chloroform, reflux 0.5 hour, put cold, wash with water 1 time, abandon water layer, get the chloroform layer evaporate to dryness, residue 0.2ml anhydrous alcohol solution is as need testing solution; Extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 0.5mg, in contrast product solution in addition; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 20 μ l of above-mentioned solution, put in same silica gel G F respectively ₂₅₄On the lamellae, with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5: 30: 15: 5 is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp 254nm and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.

(3) get this preparation 10ml, use chloroform extraction 1 time, chloroform solution is concentrated into 0.5ml, makes need testing solution; Other gets Poria control medicinal material 0.5g, adds methanol 10ml, and reflux 10 minutes filters, and filtrate water bath method, residue add water 1ml dissolving, use chloroform extraction 1 time, get chloroform solution and are concentrated into 0.5ml, in contrast medical material liquid; According to Chinese Pharmacopoeia thin layer chromatography test, draw each 20 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate=1: 10 be developing solvent, launches, and taking-up is dried, and puts under the 365nm ultra-violet lamp and inspects; In the test sample chromatograph, with control medicinal material chromatograph relevant position on, the fluorescence speckle of same color is arranged.

Check:

Relative density: get syrup,, should be not less than 1.10 according to Chinese Pharmacopoeia relative density inspection technique;

PH value: get syrup,, should be 3.0～5.0 according to Chinese Pharmacopoeia pH value inspection technique;

Other: should meet every regulation relevant under the Chinese Pharmacopoeia syrup item;

Assay: shine the Chinese Pharmacopoeia high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Acetonitrile: acetic acid: water=50: 1: 50; The detection wavelength is 283nm; Theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of reference substance solution: the naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.01mg, promptly;

The preparation of need testing solution: precision is measured this preparation 1ml, puts in the 10ml volumetric flask, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate, promptly;

Algoscopy: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.

The every 1ml of this syrup contains Exocarpium Citri Grandis with naringin C ₂₇H ₃₂O ₁₄Meter must not be less than 0.6mg.

Embodiments of the invention 10: described method of quality control can comprise:

Character: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

Differentiate: (1) gets this preparation 5ml, adds ethyl acetate 10ml jolting and extracts, and divides and gets ethyl acetate liquid, and evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets Exocarpium Citri Grandis control medicinal material 0.3 gram, adds methanol 10ml, puts in the water-bath reflux 20 minutes, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, in contrast medical material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw each 2 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate: formic acid: water=2: 3: 0.3: 0.3 is developing solvent, launch, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with 3% aluminum chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

(2) get this preparation 20ml, use chloroform extraction three times, each 15ml, chloroform solution is concentrated into 1ml, makes need testing solution; Other gets Poria control medicinal material 1g, adds methanol 20ml, and reflux 30 minutes filters, and filtrate water bath method, residue add water 5ml dissolving, use chloroform extraction three times, and each 10ml gets chloroform solution and is concentrated into about 1ml medical material liquid in contrast; According to the test of an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw each 10 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate=8: 3 is developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material chromatograph relevant position on, the fluorescence speckle of same color is arranged.

Assay: shine an appendix VID of Chinese Pharmacopoeia version in 2005 high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Methanol: acetic acid: water=35: 4: 65 is mobile phase; The detection wavelength is 283nm; Theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of the reference substance solution naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.06mg, promptly;

The preparation precision of need testing solution is measured this preparation 2ml, puts in the 50ml volumetric flask, adds methanol to scale, shakes up, and filters with 0.45 μ m microporous filter membrane, gets subsequent filtrate, promptly;

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

The every 1ml of this preparation contains Exocarpium Citri Grandis with naringin C ₂₇H ₃₂O ₁₄Meter must not be less than 1.0mg.

Embodiments of the invention 11: described method of quality control can comprise:

Character: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

Differentiate: get this preparation 30ml, the extraction 4 times that adds diethyl ether, each 20ml, discard ether layer, water layer is with water saturated n-butanol extraction 3 times, each 20ml, get n-butanol layer, evaporate to dryness adds the 5ml concentrated hydrochloric acid, the 50ml chloroform, reflux 2 hours is put cold, wash with water 3 times, each 20ml abandons water layer, get the chloroform layer evaporate to dryness, residue is with about 0.5ml anhydrous alcohol solution, as need testing solution; Extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 1mg, in contrast product solution in addition; According to the test of an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw each 4 μ l of above-mentioned solution, put in same silica gel G F respectively ₂₅₄On the lamellae, with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=10: 20: 7: 0.5 is developing solvent, launches, and takes out, and dries, and puts under the 254nm ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.

Check: pH value detects according to appendix VIIG of Chinese Pharmacopoeia version in 2005 and should be 5.0～7.0;

Relative density detects according to appendix VIIA of Chinese Pharmacopoeia version in 2005 should be not less than 1.10;

Other should meet the pertinent regulations under Chinese Pharmacopoeia version appendix I syrup in 2005 and the oral liquid item;

Assay: shine an appendix VID of Chinese Pharmacopoeia version in 2005 high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Methanol: acetic acid: water=35: 4: 65 is mobile phase; The detection wavelength is 283nm; Theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of the reference substance solution naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.06mg, promptly;

The preparation precision of need testing solution is measured this preparation 2ml, puts in the 50ml volumetric flask, adds methanol to scale, shakes up, and filters with 0.45 μ m microporous filter membrane, gets subsequent filtrate, promptly;

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

The every 1ml of this preparation contains Exocarpium Citri Grandis with naringin C ₂₇H ₃₂O ₁₄Meter must not be less than 1.0mg.

Claims (9)

1. 'Juhong Tanke ', it is characterized in that: according to part by weight, it is to be prepared from Exocarpium Citri Grandis 250-350, processed with honey Radix Stemonae 10-50, Semen Armeniacae Amarum 60-150, Fructus Schisandrae Chinensis 10-50, controlling the water circulation Rhizoma Pinelliae 10-50, Poria 10-50, Rhizoma Cynanchi Stauntonii 30-80, Radix Glycyrrhizae 5-30 and adjuvant; Wherein the used adjuvant of syrup is: 10-80% sucrose, 0.1-0.3% sodium benzoate, 0.01-0.1% ethyl hydroxybenzoate, 1-5% propylene glycol; The used adjuvant of oral liquid is: 10-50% simple syrup and 0.1-0.3% sodium benzoate, 0.01-0.1% ethyl hydroxybenzoate.

2. the preparation method of 'Juhong Tanke ' according to claim 1, it is characterized in that: the preparation method of described Juhong Tanke syrup is: Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation, collect Aromatic water, the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, Radix Glycyrrhizae Six-element, adding 5-20 times of water gaging decocts 1-5 time, each 0.5-5 hour, filter, filtrate and above-mentioned aqueous solution merge, and concentrate, add ethanol, make to contain alcohol amount and reach 40～90%, left standstill 8-50 hour, get supernatant and reclaim ethanol, concentrate, add sucrose, 0.1-0.3% sodium benzoate and the 0.01-0.1% ethyl hydroxybenzoate of preparation total amount 10-80%, heating for dissolving is put cold, add above-mentioned Aromatic water and 1-5% propylene glycol, mixing adds water to 1000ml, promptly.

3. the preparation method of 'Juhong Tanke ' according to claim 1, it is characterized in that: the preparation method of described red tangerine peel oral liquor for treating productive cough is: Exocarpium Citri Grandis, Semen Armeniacae Amarum vapor distillation, collect Aromatic water, the aqueous solution after the distillation filters standby; The medicinal residues and the controlling the water circulation Rhizoma Pinelliae, the processed with honey Radix Stemonae, Fructus Schisandrae Chinensis, Poria, Rhizoma Cynanchi Stauntonii, the Radix Glycyrrhizae Six-element adds 5-20 times of water gaging and decocts 1-5 time, each 0.5-5 hour, filter, filtrate and above-mentioned aqueous solution merge, and concentrate, add ethanol, make to contain alcohol amount and reach 40～90%, left standstill 8-50 hour, get supernatant and reclaim ethanol, concentrate, add water to the 40-100% of total amount, 4 ℃～8 ℃ cold preservation 30-100h filter, filtrate adds simple syrup to sugar content 10-50%, add the 0.1-0.3% sodium benzoate, the 0.01-0.1% ethyl hydroxybenzoate boils dissolving, adds water to 1000ml, stir evenly, filter, embedding, promptly.

4. the method for quality control of 'Juhong Tanke ' as claimed in claim 1, described preparation comprises syrup and oral liquid, it is characterized in that: described method of quality control mainly comprise in character, discriminating, inspection and the assay project partly or entirely; Wherein differentiate the thin layer chromatography discriminating that comprises Exocarpium Citri Grandis, Radix Glycyrrhizae and Poria in the preparation; Assay is that the contained naringin of Exocarpium Citri Grandis in the preparation is carried out assay.

5. according to the method for quality control of the described 'Juhong Tanke ' of claim 4, it is characterized in that: the discrimination method of Exocarpium Citri Grandis is to be contrast with the Exocarpium Citri Grandis control medicinal material, and with toluene: ethyl acetate: formic acid: water=1-10: 1-10: 0.1-5: 0.1-5 is the thin layer chromatography of developing solvent; The discrimination method of Radix Glycyrrhizae is to be contrast with the enoxolone reference substance, and with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-20: 10-30: 1-15: 0.1-5 is the thin layer chromatography of developing solvent; The discrimination method of Poria is to be contrast with the Poria control medicinal material, is the thin layer chromatography of developing solvent with toluene: ethyl acetate=1-20: 0.5-10.

6. according to the method for quality control of the described 'Juhong Tanke ' of claim 5, it is characterized in that: concrete discrimination method comprises the part or all of of following project:

(1) get this preparation 1-10ml, add ethyl acetate 5-50ml jolting and extract, divide and get ethyl acetate liquid, evaporate to dryness, residue add dehydrated alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets Exocarpium Citri Grandis control medicinal material 0.1-1 gram, adds methanol 5-50ml, puts in the water-bath reflux 10-100 minute, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 0.5-3ml makes dissolving, in contrast medical material solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 1-10 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate: formic acid: water=1-10: 1-10: 0.1-5: 0.1-5 is developing solvent, launch, take out, dry, spray is put under the ultra-violet lamp 365nm and is inspected with 3% aluminum chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

(2) get this preparation 10-100ml, extraction 1-8 time that adds diethyl ether discards ether layer, water layer is got n-butanol layer, evaporate to dryness with water saturated n-butanol extraction 1-5 time, add the 1-10ml concentrated hydrochloric acid, 10-100ml chloroform, reflux 0.5-5 hour, put cold, wash with water 1-5 time, abandon water layer, get the chloroform layer evaporate to dryness, residue 0.2-2ml anhydrous alcohol solution is as need testing solution; Extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 2-20 μ l of above-mentioned solution, put respectively on same silica GF254 lamellae, with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-20: 10-30: 1-15: 0.1-5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

(3) get this preparation 10-100ml, use chloroform extraction 1-6 time, chloroform solution is concentrated into 0.5-5ml, makes need testing solution; Other gets Poria control medicinal material 0.5-3g, adds methanol 10-50ml, and reflux 10-100 minute, filter, filtrate water bath method, residue add water 1-20ml dissolving, use chloroform extraction 1-6 time, get chloroform solution and are concentrated into 0.5-3ml, in contrast medical material liquid; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 5-20 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, be developing solvent with toluene: ethyl acetate=1-20: 0.5-10, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material chromatograph relevant position on, the fluorescence speckle of same color is arranged.

7. according to the method for quality control of the described 'Juhong Tanke ' of claim 4, it is characterized in that: the content assaying method of naringin is to be contrast with the naringin reference substance in the Exocarpium Citri Grandis, and with methanol or acetonitrile: acetic acid: water=20-50: 1-10: 50-80 is the high performance liquid chromatography of mobile phase.

8. according to the method for quality control of claim 4 or 7 described 'Juhong Tanke 's, it is characterized in that: concrete content assaying method is:

According to the Chinese Pharmacopoeia high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol or acetonitrile: acetic acid: water=20-50: 1-10: 50-80; The detection wavelength is 283nm; Theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of reference substance solution: the naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.01-0.5mg, promptly;

The preparation of need testing solution: precision is measured this preparation 1-10ml, puts in the 10-100ml volumetric flask, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate, promptly;

Algoscopy: accurate respectively reference substance solution and each 5-20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly;

The every 1ml of syrup contains Exocarpium Citri Grandis in naringin C27H32O14 in this preparation, must not be less than 0.6mg; The every 1ml of oral liquid contains Exocarpium Citri Grandis in naringin C27H32O14, must not be less than 0.3mg.

9. according to the method for quality control of the described 'Juhong Tanke ' of claim 4, it is characterized in that: described method of quality control comprises:

Character:

For syrup: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

For oral liquid: product is that sundown is to tan liquid; It is sweet to distinguish the flavor of, little hardship;

Differentiate: (1) gets this preparation 1-10ml, adds ethyl acetate 5-50ml jolting and extracts, and divides and gets ethyl acetate liquid, and evaporate to dryness, residue add dehydrated alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets Exocarpium Citri Grandis control medicinal material 0.1-1 gram, adds methanol 5-50ml, puts in the water-bath reflux 10-100 minute, filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 0.5-3ml makes dissolving, in contrast medical material solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 1-10 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate: formic acid: water=1-10: 1-10: 0.1-5: 0.1-5 is developing solvent, launch, take out, dry, spray is put under the ultra-violet lamp 365nm and is inspected with 3% aluminum chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

(2) get this preparation 10-100ml, extraction 1-8 time that adds diethyl ether discards ether layer, water layer is got n-butanol layer, evaporate to dryness with water saturated n-butanol extraction 1-5 time, add the 1-10ml concentrated hydrochloric acid, 10-100ml chloroform, reflux 0.5-5 hour, put cold, wash with water 1-5 time, abandon water layer, get the chloroform layer evaporate to dryness, residue 0.2-2ml anhydrous alcohol solution is as need testing solution; Extracting liquorice subacid reference substance adds dehydrated alcohol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 2-20 μ l of above-mentioned solution, put respectively on same silica GF254 lamellae, with 60～90 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-20: 10-30: 1-15: 0.1-5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

(3) get this preparation 10-100ml, use chloroform extraction 1-6 time, chloroform solution is concentrated into 0.5-5ml, makes need testing solution; Other gets Poria control medicinal material 0.5-3g, adds methanol 10-50ml, and reflux 10-100 minute, filter, filtrate water bath method, residue add water 1-20ml dissolving, use chloroform extraction 1-6 time, get chloroform solution and are concentrated into 0.5-3ml, in contrast medical material liquid; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 5-20 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, be developing solvent with toluene: ethyl acetate=1-20: 0.5-10, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material chromatograph relevant position on, the fluorescence speckle of same color is arranged;

Check:

Relative density: get syrup,, should be not less than 1.10 according to Chinese Pharmacopoeia relative density inspection technique;

PH value: get syrup or oral liquid,, should be 3.0～7.0 according to Chinese Pharmacopoeia pH value inspection technique;

Other: should meet every regulation relevant under Chinese Pharmacopoeia syrup or the mixture item;

Assay: shine the Chinese Pharmacopoeia high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol or acetonitrile: acetic acid: water=20-50: 1-10: 50-80; The detection wavelength is 283nm; Theoretical cam curve is calculated by the naringin peak should be not less than 2000;

The preparation of reference substance solution: the naringin reference substance that is dried to constant weight of learning from else's experience 110 ℃ is an amount of, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.01-0.5mg, promptly;

The preparation of need testing solution: precision is measured this preparation 1-10ml, puts in the 10-100ml volumetric flask, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate, promptly;

Algoscopy: accurate respectively reference substance solution and each 5-20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly;

The every 1ml of syrup contains Exocarpium Citri Grandis in naringin C27H32O14 in this preparation, must not be less than 0.6mg; The every 1ml of oral liquid contains Exocarpium Citri Grandis in naringin C27H32O14, must not be less than 0.3mg.