CN1698757A - Pharmaceutical preparation for treating upper respiratory tract infection and its preparation process and quality control method - Google Patents
Pharmaceutical preparation for treating upper respiratory tract infection and its preparation process and quality control method Download PDFInfo
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Abstract
The invention relates to a pharmaceutical preparation for treating upper respiratory tract infection and its preparation process and quality control method, wherein the preparation is in the form of injection or oral liquid prepared from goldthread root, rhubarb horsetails, baikal skullcap and other auxiliary materials.
Description
Technical field: the present invention is a kind of pharmaceutical preparation of YIQING and method for making and quality control method for the treatment of upper respiratory tract infection, belongs to technical field of Chinese medicine.
Technical background: the compound Chinese medicinal preparation that a clear preparation is made up of Chinese medicines such as Rhizoma Coptidis, Radix Scutellariae, Radix Et Rhizoma Rhei, effect with clearing away heat-fire detoxifcation, blood stasis dispelling removing heat from blood, hemostasis, report can be used for treating hypertension due to acute and chronic upper respiratory tract infection, treatment of allergic rhinitis, treatment constipation and enteritis, treatment carbuncle sore tumefacting virus, oral ulcer, gingival swelling and pain, burn due to hot liquid or fire, treatment acute icterohepatitisshock, treatment bleeding hemorrhoids, the treatment hyperlipemia, and auxiliary treatment chronic kidney disease etc. clinically.A large amount of research has been done to it by many inventors and medicine enterprise, and the product of some treatments also is provided; As a YIQING KELI of having gone on the market and a clearing capsule, but should side's medicine taste extremely bitter, granule have added a large amount of sucrose flavorings, be not suitable for diabetics and take for a long time; One clearing capsule, disintegrate is slow, and bioavailability is low, medicine stability is undesirable.Baicalin is the main component of said preparation, and modern pharmacological research shows that baicalin has effects such as stronger antibiotic, antiinflammatory.But baicalin water solublity little (1.2mg/100ml), absorption difference, and character instability, therefore easy oxidation deterioration makes the subject matter of its preparation bioavailability difference foot existing product.And the applicant is being " 03124462.9 " to the disclosed number of patent application of Chinese patent gazette, name is called " a clear ball and a preparation method ", number of patent application is " 02113597.5 ", name is called " a kind of improvement preparation technology who treats the Chinese medicinal capsule of constipation ", number of patent application is " 200410038829.7 ", name is called the patent application of " a kind of preparation method of Chinese medicinal soft capsule preparation and method of quality control " and carries out finding in the research process, the pill shelf-life is shorter, is unfavorable for the storage and the transportation of medicine; Soft capsule is higher slightly than the disintegration of conventional capsule, but because the rubber problem of aging, the disintegrate delay phenomenon often occurs, so mainly be that the baicalin of one of effective ingredient still is not very desirable in absorption by human body; Improved capsule technique improves disintegration by spray drying, but does not have spray-dired technological parameter, concrete technology, can't implement at all.In view of such circumstances, need to seek a kind of therapeutic effect ideal, technology advanced person, the new pharmaceutical preparation that bioavailability is high and the preparation method of this preparation.
Summary of the invention: the objective of the invention is to: a kind of pharmaceutical preparation and method for making and quality control method for the treatment of upper respiratory tract infection is provided; Be prepared into and disperse sheet, dropping pill formulation; Dispersible tablet provided by the invention adopts the micropill granulation technique, and the product disintegrative is good, has improved the bioavailability of effective ingredient, is particularly suitable for the old people and swallow tablet or the inconvenient patient of capsule take; Drop pill provided by the invention adopts drop pill gradient cooling technology, improves drug bioavailability, increases medicine dissolution, moisture resistance; And technical maturity is stable, is beneficial to penetration and promotion.
The present invention constitutes like this: it is to be made into injection, powder pin, freeze-dried powder, gel, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, micropill, powder, drop pill, slow releasing preparation, controlled release preparation, gel, oral liquid, soft extract, extractum or membrane by Rhizoma Coptidis 165g, Radix Et Rhizoma Rhei 500g, Radix Scutellariae 250g and adjuvant.Specifically: the preparation of the present invention's preparation is drop pill, dispersible tablet or soft capsule.
Described preparation method: get Rhizoma Coptidis, Radix Et Rhizoma Rhei, Radix Scutellariae, decoct with water secondary respectively, 1.5 hours for the first time, 1 hour for the second time, collecting decoction filtered, filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃, is spray dried to dry extract, makes other preparations again.
Drop pill in the described preparation prepares like this: get Rhizoma Coptidis, Radix Et Rhizoma Rhei, Radix Scutellariae, decoct with water secondary respectively, 1.5 hours for the first time, 1 hour for the second time, collecting decoction filters, and filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃, be spray dried to dry extract, with the polyoxyethylene monostearate is substrate, and the proportioning of medicine and substrate is 1: 1.5, mixing, splash in the coolant methyl-silicone oil, dripping the system footpath is the dropper of 6.1mm, and 20～30/min splashes in the long cooling column of 120cm, adopts the gradient cooling, the Temperature Distribution of gradient liquid coolant is 40 ℃～50 ℃, 20 ℃～30 ℃, 0 ℃～4 ℃, promptly.
Dispersible tablet in the described preparation prepares like this: get Rhizoma Coptidis, Radix Et Rhizoma Rhei, Radix Scutellariae, decoct with water secondary respectively, 1.5 hours for the first time; 1 hour for the second time; collecting decoction filters, and filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃; be spray dried to dry extract; add by medicine: the adjuvant ratio is 3: 1 a microcrystalline Cellulose, crosses the abundant mixing of 60 mesh sieves, and adding concentration is that 50% ethanol is that wetting agent is made soft material; employing is extruded-round as a ball comminutor, extrudes rotating speed 30rmin
-1, round as a ball 5min, round as a ball rotating speed 550rmin
-1, make micropill, in 50 ℃ of bakings 12 hours, take out, add by medicine: the adjuvant ratio is 2: 1 low-substituted hydroxypropyl cellulose, by medicine: the adjuvant ratio is 1: 1 a carboxymethyl starch sodium, mix homogeneously, and mistake is sieved for No. 5, make wetting agent system soft material with the 5%PVP alcoholic solution, cross the sieve series grain No. 2,60 ℃ of oven dry, No. 2 sieve granulate, add simultaneously in medicine: the adjuvant ratio is a tabletting behind 1: 2 the low-substituted hydroxypropyl cellulose mixing, promptly.
The assay of the method for quality control of described pharmaceutical preparation is an index with baicalin, chrysophanic acid, berberine; Discriminating is a reference substance with emodin, berberine hydrochloride, baicalin.
Described pharmaceutical preparation assay is such: with methanol-0.2mol/L phosphate sodium dihydrogen buffer solution, regulate pH value to 2.7 with phosphoric acid, (42: 58) are mobile phase; The detection wavelength is 275nm; Precision takes by weighing the baicalin reference substance 12.5mg that is dried to constant weight at 105 ℃, puts in the 250ml measuring bottle, with the small amount of methanol dissolving, is diluted to scale with double distilled water, shakes up, and promptly gets the reference substance solution that contains baicalin 50 μ g among every 1ml; Get the content under this product content uniformity item, mixing, porphyrize, get about 0.75g, the accurate title, decide, and puts in the 100ml measuring bottle, adds methanol 10ml, supersound process 10 minutes, be diluted to scale with double distilled water, got this liquid centrifugal 10 minutes, the per minute rotating speed is 15000 commentaries on classics, divide and get supernatant, promptly get need testing solution; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure.
It is such that described pharmaceutical preparation is differentiated:
(1) gets this product 8g, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 30 minutes, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution.Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 10 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, upper solution with petroleum ether-Ethyl formates of 60～90 ℃-formic acid=15: 5: 1 is developing solvent, launch, take out, dry, it is smoked clear to the speckle colour developing to put in the ammonia steam.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical punctation;
(2) get this product 8g, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 20 minutes filters, and filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution.Test according to thin layer chromatography, draw each 10 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 ethyl acetate-butanone-formic acid-water=10: 6: 1: 1 was developing solvent, launch, take out, dry, spray is with 2% ferric chloride alcoholic solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical aeruginous speckle;
(3) get this product 8g, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution.Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution.According to thin layer chromatography test, draw each 10 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 ethyl acetate-butanone-formic acid-water=10: 6: 1: 1 was developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical yellow fluorescence speckle.
Compared with prior art, the present invention has overcome the problem that existing product exists, the dispersible tablet that provides, and disintegrative is good, and dissolution is good; And the drop pill that provides can be covered poor taste, the abnormal smells from the patient of medicine, and plays the effect that increases stability, improves bioavailability; The formulation products that obtains has the effect of clearing away heat-fire detoxifcation, blood stasis dispelling removing heat from blood, hemostasis, is used for the treatment of hypertension due to acute and chronic upper respiratory tract infection, treatment of allergic rhinitis, treatment constipation and enteritis, treatment carbuncle sore tumefacting virus, oral ulcer, gingival swelling and pain, burn due to hot liquid or fire, treatment acute icterohepatitisshock, treatment bleeding hemorrhoids, the treatment hyperlipemia, and auxiliary treatment chronic kidney disease etc.Utilize preparation method provided by the invention can solve the existing shortcoming that exists of producing, the preparation that both economical, rational preparation needs; Utilize method of quality control provided by the invention can guarantee the formulation science of preparation, effectively; The present invention has reached the purpose of invention.
In the process of development drop pill, find that the roundness difference and the hygroscopicity of this product are stronger.Find after deliberation because the condensation column upper temp is lower, can make some bubbles of bringing in the drop when overflowing, produce empty or when overflowing bubble the medicinal liquid of being with do not withdraw as yet and form tail, cause roundness poor; The applicant adopts the gradient cooling, and the Temperature Distribution of liquid coolant is 40 ℃～50 ℃, 20 ℃～30 ℃, 0 ℃～4 ℃, makes the roundness of product be improved.
Find that in the process of development dispersible tablet dispersing uniformity is maximum difficult point.The applicant adopts the micropill granulation technique, and add by medicine: the adjuvant ratio is 3: 1 a microcrystalline Cellulose, crosses the abundant mixing of 60 mesh sieves, and adding concentration and be 50% ethanol is that wetting agent is made soft material, and employing is extruded-round as a ball comminutor, extrudes rotating speed 30rmin
-1, round as a ball 5min, round as a ball rotating speed 550rmin
-1, make micropill, in 50 ℃ of bakings 12 hours, take out, add by medicine: the adjuvant ratio is 2: 1 low-substituted hydroxypropyl cellulose, by medicine: the adjuvant ratio is 1: 1 a carboxymethyl starch sodium, mix homogeneously, and mistake is sieved for No. 5, make wetting agent system soft material with the 5%PVP alcoholic solution, cross the sieve series grain No. 2,60 ℃ of oven dry, No. 2 sieve granulate, add simultaneously in medicine: the adjuvant ratio is a tabletting behind 1: 2 the low-substituted hydroxypropyl cellulose mixing, and the dispersible tablet quality that makes is good; So by a series of experiments, with the supplementary product kind of the preparation technology that selects pharmaceutical preparation provided by the invention, use and consumption, ratio etc.; Guarantee its science, reasonable, feasible; The preparation that obtains has effective therapeutic effect.
Experimental example 1: Study on Forming
(1) dispersible tablet Study on Forming
Dispersible tablet meet water rapidly disintegrate form the water dispersion tablet of uniform sticky suspension, it is poor to have solved former dosage form disintegrative, stripping is shortcoming slowly, and the dispersible tablet that the applicant makes is disintegrate fully in the 3min in 19 ℃～21 ℃ water, and suspension ability is good, bioavailability is high, dispersed homogeneous degree.
The mensuration of dispersing uniformity: with reference to Chinese Pharmacopoeia version appendix in 2000 IA, get 6 of dispersible tablets, place the jolting of 100ml water, in (20 ± 1) ℃ water, the whole disintegrates of 3min planted agent are also passed through sieve No. 2.
1. micropill granulating process research
Take by weighing the 40g micropill, pour into lightly in the graduated cylinder of 100mL, fall repeatedly from the 5cm eminence then, no longer change up to volume, the recording volume number calculates bulk density.
The round as a ball rotating speed rmin of the round as a ball time min of group concentration of alcohol %
-1Bulk density gmL
-1
1 30 5 550 0.60
2 30 8 700 0.62
3 40 5 550 0.70
4 40 8 700 0.71
5 50 5 550 0.83
6 50 8 700 0.70
The result shows, the optimum process that the present invention prepares micropill is that 50% ethanol is that wetting agent is made soft material for adding concentration, adopts and extrudes-round as a ball comminutor round as a ball 5min, round as a ball rotating speed 550rmin
-1
2. tablet forming technique research
Group low-substituted hydroxypropyl cellulose low-substituted hydroxypropyl cellulose carboxymethyl starch sodium PVP alcoholic solution dispersing uniformity
In add (medicine: adjuvant) add (medicine: (medicine: concentration % adjuvant) adjuvant)
1 1.5: 11: 12: 16 become sticking group
2 1.5: 1-2: 16 thicker
3 1.5: 11: 1-5 thicker
41: 22: 11: 15 is qualified
51: 2-1: 14 thicker
61: 22: 1-4 becomes sticking group
The result shows, optimum process condition is for by medicine: the adjuvant ratio is 2: 1 adding low-substituted hydroxypropyl celluloses, in medicine: the adjuvant ratio is 1: 1 a carboxymethyl starch sodium, mix homogeneously, cross sieve No. 5, make wetting agent system soft material with the 5%PVP alcoholic solution, cross No. 2 sieve series grains, 60 ℃ of oven dry, No. 2 sieve granulate add simultaneously in medicine: the adjuvant ratio is a tabletting behind 1: 2 the low-substituted hydroxypropyl cellulose mixing.
3. check disintegration
Group disintegrate/molten diffusing time
Ordinary tablet 40.8min
Pill 58.1min
Capsule 35.5min
The dispersible tablet 4.9min that granulates of micropill not
Dispersible tablet 58sec of the present invention
The result shows that micropill makes dispersible tablet after granulating, and makes medicine increase at the area on gastrointestinal tract surface, has solved granule and has met the sticking problem that influences disintegrate of waterishlogging, has improved bioavailability of medicament.
(2) drop pill Study on Forming
Drip the system technical study
Group coolant cools mode cooling column height/cm roundness qualification rate %
1 methyl-silicone oil gradient 120 92.53
2 methyl-silicone oil gradients 120 87.59
The non-gradient 160 85.34 of 3 liquid paraffin
The non-gradient 160 82.67 of 4 liquid paraffin
The result shows, with the polyoxyethylene monostearate is substrate, the proportioning of medicine and substrate is 1: 1.5, mixing, splash in the coolant methyl-silicone oil, dripping the system footpath is the dropper of 6.1mm, and 20～30/min splashes in the long cooling column of 120cm, the cooling of employing gradient, the Temperature Distribution of gradient liquid coolant is 40 ℃～50 ℃, 20 ℃～30 ℃, 0 ℃～4 ℃.
Bioavailability relatively
The SD rat, body weight 250～280g, male and female half and half, fasting overnight (can't help water), next day gastric infusion, dosage is 3.8g/kg.15min before administration and after the administration, 30min, 50min, 80min, 2h, 3h, the blood sampling of 4h and 8h heart, each blood sample point is with 6 rats.Blood sample is put the anticoagulant heparin pipe, the centrifugal 5min of 3000r/min, and separated plasma is put-30 ° and is saved to analysis.High performance liquid chromatograph is by the M510 pump, the U6K injector, and M490 variable-wavelenght detector and 810 chromatographic data treating stations are formed (Waters, the U.S.).Analytical column is μ BondpakaC
18(0.45mm * 25cm); Mobile phase is methanol: water=6: 4; Flow velocity: 0.8mL/min; Detect wavelength: λ=230nm.Baicalin extracts in the blood plasma: get 0.5mL blood plasma, add 5mLCHCl
3, interior mark 50 μ L, test tube is done 30 ° and is favoured horizontal direction jolting device, and 15min is extracted in jolting, centrifugal (3000r/min) 10min, aqueous phase discarded, the accurate 4mL organic facies of drawing is in a clean tube, at 37 ℃ of water-baths, N
2Dry up under the air-flow, residue dissolves the sample introduction analysis again with 200 μ L mobile phases.
Rat plasma baicalin concentration change (N=6)
Time/h blood plasma baicalin concentration/(mgL
-1)
Soft capsule drop pill of the present invention dispersible tablet of the present invention
0 - - - - -
0.25 1.01±0.15 1.62±0.15 1.73±0.28
0.50 1.95±0.72 3.57±1.19 3.32±1.10
0.83 2.02±0.53 2.22±0.38 2.30±0.28
1.33 1.20±0.61 1.68±0.67 1.74±0.42
2.00 0.88±0.28 1.24±0.25 1.39±0.25
3.00 0.96±0.22 1.05±0.17 1.03±0.18
4.00 0.46±0.17 0.81±0.24 0.83±0.15
6.00 0.17±0.02 0.54±0.19 0.45±0.27
8.00 0.05±0.11 0.24±0.10 0.26±0.13
The result shows that the bioavailability of product of the present invention is greater than soft capsule.
Experimental example 2: pharmacodynamic experiment
1, the research of antiinflammatory action
Adopt the scorching method of caused by dimethylbenzene xylene, observe the influence that xylol causes mouse right ear swelling, get 70 of healthy mices, body weight 20 ± 2g, be divided into 7 groups at random, every group 10, male and female half and half, i.e. blank group (normal saline group), positive controls (aspirin group), YIQING KELI group, drop pill group of the present invention, dispersible tablet group of the present invention.The listed dosage grouping of according to the form below gastric infusion, every day 1 time, successive administration 3 days, medicine group administration cubical content is the 20ml/kg body weight, and negative control group is given normal saline 10ml/kg body weight.Last was irritated stomach after 30 minutes, and only evenly being applied in the mouse ear two sides causes inflammation with dimethylbenzene 0.05ml, and left ear is not coated with dimethylbenzene in contrast.Putting to death mice after 45 minutes, cut ears along baseline, is that the card punch of 5mm sweeps away the both sides auricle respectively with diameter, with the analytical balance contrast of weighing.With about the heavy difference of two auricle sheets as the swelling degree, and calculate inhibitory rate of intumesce.
Influence to mice caused by dimethylbenzene xylene ear inflammation
Group dosage (g/kg) Mus number (only) swelling degree (mg) suppression ratio (%)
Normal saline group---10 10.37 ± 5.09---
YIQING KELI group 10 10 5.34 ± 3.51 48.51
Drop pill group 10 10 4.64 of the present invention ± 2.38 55.26
Dispersible tablet group 10 10 4.42 of the present invention ± 4.03 57.38
Aspirin group 0.6 10 2.79 ± 1.52 73.10
The result shows that drop pill of the present invention, dispersible tablet of the present invention have obvious inhibitory action to mice caused by dimethylbenzene xylene ear inflammation, and effect is better than commercially available YIQING KELI.
2, to the research of intestinal propulsion effect
Get 60 of Kunming mouses, body weight 20 ± 2g, male and female half and half, fasting 12h before the experiment.Mice is divided into 6 groups at random: matched group, YIQING KELI group, drop pill group of the present invention, dispersible tablet of the present invention.Matched group gives 0.5% sodium carboxymethyl cellulose, all irritates stomach by body constitution amount 20ml/kg.30min gives the suspension that each Mus 5% carbon is not made with 10% arabic gum behind the medicine, irritates stomach by body constitution amount 10ml/kg, puts to death animal with the cervical vertebra dislocation method behind the 30min, carve abdomen immediately, with the digestive tract complete excision of pylorus to rectum end, do not add traction, be tiled on the glass plate.Measure intestinal total length and carbon powder forward position distance, calculate the percentage rate that the latter accounts for the intestinal total length to pylorus.Computing formula is: charcoal end advance (%)=charcoal forward position, end and pylorus distance (cm) * 100%/small intestinal total length (pylorus is to ileocecus) (cm).Concrete outcome sees the following form
Influence to the mouse small intestine progradation
Group dosage (g/kg) charcoal end advances (%)
Matched group 0 36.4 ± 6.8
YIQING KELI group 10 53.1 ± 9.6
Drop pill group 10 56.8 ± 10.6 of the present invention
Dispersible tablet group 10 55.2 ± 8.2 of the present invention
The result shows, 30min can make mouse intestinal carbon powder fltting speed significantly increase (to account for intestinal percentage ratio be not index in the forward position with carbon) after YIQING KELI, drop pill of the present invention, the dispersible tablet administration of the present invention; The effect of preparation of the present invention is better than commercially available YIQING KELI.
3. to the research of anastalsis
Adopt the docking method to carry out hemostasis trial, get 60 of healthy mices, body weight 20 ± 2g is divided into 6 groups at random, and 10 every group, male and female half and half, i.e. matched group (normal saline group), a clearing capsule group, drop pill group of the present invention, dispersible tablet group of the present invention.The medicine group is pressed the volume of 20ml/kg body weight and is irritated stomach, and the filling stomach volume of normal saline group is the 10ml/kg body weight; Administration every day 1 time, successive administration 3 days.After the last administration, the about 1cm of mice Mus point place cut off in 30 minutes, in the record bleeding time, dehematized with the filter paper suction in per 15 seconds, droplet for 1 time until stopped bleeding.Gained result and data see the following form.
Anastalsis to mice
Group dosage (g/kg) Mus number (only) stops the bleeding time (min)
The normal saline group---10 17.5 ± 4.67
One clearing capsule group 10 10 9.18 ± 3.42
Drop pill group 10 10 7.86 ± 2.10 of the present invention
Dispersible tablet group 10 10 8.23 ± 4.56 of the present invention
Experimental result shows, compares with normal saline, and YIQING KELI, drop pill of the present invention, dispersible tablet of the present invention are to the sharp hemorrhage good anastalsis that has of mice Mus.
Concrete embodiment:
Embodiments of the invention 1: get Rhizoma Coptidis 165g, Radix Et Rhizoma Rhei 500g, Radix Scutellariae 250g, decoct with water secondary respectively, 1.5 hours for the first time, 1 hour for the second time, collecting decoction, filter, filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃, being spray dried to dry extract, is substrate with the polyoxyethylene monostearate, and the proportioning of medicine and substrate is 1: 1.5, mixing, splash in the coolant methyl-silicone oil, dripping the system footpath is the dropper of 6.1mm, and 20～30/min splashes in the long cooling column of 120cm, the cooling of employing gradient, the Temperature Distribution of gradient liquid coolant is 40 ℃～50 ℃, 20 ℃～30 ℃, 0 ℃～4 ℃, promptly get drop pill, this product oral, three times on the one, each 2-4 grain.
Embodiments of the invention 2: get Rhizoma Coptidis 165g, Radix Et Rhizoma Rhei 500g, Radix Scutellariae 250g, decoct with water secondary respectively, 1.5 hours for the first time; 1 hour for the second time; collecting decoction filters, and filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃; be spray dried to dry extract; add by medicine: the adjuvant ratio is 3: 1 a microcrystalline Cellulose, crosses the abundant mixing of 60 mesh sieves, and adding concentration is that 50% ethanol is that wetting agent is made soft material; employing is extruded-round as a ball comminutor, extrudes rotating speed 30rmin
-1, round as a ball 5min, round as a ball rotating speed 550rmin
-1, make micropill, in 50 ℃ of bakings 12 hours, take out, add by medicine: the adjuvant ratio is 2: 1 low-substituted hydroxypropyl cellulose, by medicine: the adjuvant ratio is 1: 1 a carboxymethyl starch sodium, mix homogeneously, and mistake is sieved for No. 5, make wetting agent system soft material with the 5%PVP alcoholic solution, cross the sieve series grain No. 2,60 ℃ of oven dry, No. 2 sieve granulate, add simultaneously in medicine: the adjuvant ratio is a tabletting behind 1: 2 the low-substituted hydroxypropyl cellulose mixing, promptly gets dispersible tablet.
Embodiments of the invention 3: get Rhizoma Coptidis 165g, Radix Et Rhizoma Rhei 500g, Radix Scutellariae 250g, decoct with water secondary respectively, 1.5 hours for the first time, 1 hour for the second time, collecting decoction, filter, filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃, is spray dried to dry extract, adds water for injection, syrup, make 1000 bottles, promptly get oral liquid.
Embodiments of the invention 4: get Rhizoma Coptidis 165g, Radix Et Rhizoma Rhei 500g, Radix Scutellariae 250g, decoct with water secondary respectively, 1.5 hours for the first time, 1 hour for the second time, collecting decoction, filter, filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃, is spray dried to dry extract, add carbomer solution, correctives, stir evenly, make 1000 bottles, promptly get gel.
Embodiments of the invention 5: assay
With methanol-0.2mol/L phosphate sodium dihydrogen buffer solution, regulate pH value to 2.7 with phosphoric acid, (42: 58) are mobile phase; The detection wavelength is 275nm; Precision takes by weighing the baicalin reference substance 12.5mg that is dried to constant weight at 105 ℃, puts in the 250ml measuring bottle, with the small amount of methanol dissolving, is diluted to scale with double distilled water, shakes up, and promptly gets the reference substance solution that contains baicalin 50 μ g among every 1ml; Get the content under this product content uniformity item, mixing, porphyrize, get about 0.75g, the accurate title, decide, and puts in the 100ml measuring bottle, adds methanol 10ml, supersound process 10 minutes, be diluted to scale with double distilled water, got this liquid centrifugal 10 minutes, the per minute rotating speed is 15000 commentaries on classics, divide and get supernatant, promptly get need testing solution; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure.
Embodiments of the invention 6: differentiate
(1) gets this product 8g, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 30 minutes, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution.Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 10 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, upper solution with petroleum ether-Ethyl formates of 60～90 ℃-formic acid=15: 5: 1 is developing solvent, launch, take out, dry, it is smoked clear to the speckle colour developing to put in the ammonia steam.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical punctation;
(2) get this product 8g, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 20 minutes filters, and filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution.Test according to thin layer chromatography, draw each 10 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 ethyl acetate-butanone-formic acid-water=10: 6: 1: 1 was developing solvent, launch, take out, dry, spray is with 2% ferric chloride alcoholic solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical aeruginous speckle;
(3) get this product 8g, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution.Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution.According to thin layer chromatography test, draw each 10 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 ethyl acetate-butanone-formic acid-water=10: 6: 1: 1 was developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical yellow fluorescence speckle.
Claims (8)
1, the pharmaceutical preparation of YIQING of treatment upper respiratory tract infection, it is characterized in that: it is to be made into injection, powder pin, freeze-dried powder, gel, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, micropill, powder, drop pill, slow releasing preparation, controlled release preparation, gel, oral liquid, soft extract, extractum or membrane with Rhizoma Coptidis 165g, Radix Et Rhizoma Rhei 500g, Radix Scutellariae 250g and adjuvant.
2, according to the pharmaceutical preparation of YIQING of the described treatment upper respiratory tract infection of claim 1, it is characterized in that: described preparation is drop pill, dispersible tablet or pellet.
3, treat the preparation method of the pharmaceutical preparation of YIQING of upper respiratory tract infection as claimed in claim 1 or 2, it is characterized in that: get Rhizoma Coptidis, Radix Et Rhizoma Rhei, Radix Scutellariae, decoct with water secondary respectively, 1.5 hours for the first time, 1 hour for the second time, collecting decoction, filter, filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃, is spray dried to dry extract, makes other preparations again.
4, preparation method according to the pharmaceutical preparation of YIQING of the described treatment upper respiratory tract infection of claim 3, it is characterized in that: the drop pill in the described preparation prepares like this: get Rhizoma Coptidis, Radix Et Rhizoma Rhei, Radix Scutellariae, decoct with water secondary respectively, 1.5 hours for the first time, 1 hour for the second time, collecting decoction, filter, filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃, is spray dried to dry extract, is substrate with the polyoxyethylene monostearate, the proportioning of medicine and substrate is 1: 1.5, mixing splashes in the coolant methyl-silicone oil, and dripping the system footpath is the dropper of 6.1mm, 20～30/min splashes in the long cooling column of 120cm, the cooling of employing gradient, the Temperature Distribution of gradient liquid coolant is 40 ℃～50 ℃, 20 ℃～30 ℃, 0 ℃～4 ℃, promptly.
5; the preparation method of the pharmaceutical preparation of YIQING of treatment upper respiratory tract infection as claimed in claim 3; it is characterized in that: the dispersible tablet in the described preparation prepares like this: get Rhizoma Coptidis; Radix Et Rhizoma Rhei; Radix Scutellariae; decoct with water secondary respectively; 1.5 hours for the first time; 1 hour for the second time; collecting decoction; filter; filtrate decompression is concentrated into relative density and is about 1.25 for 70 ℃, is spray dried to dry extract, and add in medicine: the adjuvant ratio is 3: 1 a microcrystalline Cellulose; cross the abundant mixing of 60 mesh sieves; adding concentration and be 50% ethanol is that wetting agent is made soft material, adopts and extrudes-round as a ball comminutor, extrudes rotating speed 30rmin
-1,, round as a ball 5min, round as a ball rotating speed 550rmin
-1,, make micropill, in 50 ℃ of bakings 12 hours, take out, add in medicine: the adjuvant ratio is 2: 1 low-substituted hydroxypropyl cellulose, in medicine: the adjuvant ratio is 1: 1 a carboxymethyl starch sodium, mix homogeneously, cross sieve No. 5, make wetting agent system soft material, cross No. 2 sieve series grains with the 5%PVP alcoholic solution, 60 ℃ of oven dry, No. 2 sieve granulate add simultaneously in medicine: the adjuvant ratio is a tabletting behind 1: 2 the low-substituted hydroxypropyl cellulose mixing, promptly.
6, the method for quality control of the pharmaceutical preparation of YIQING of treatment upper respiratory tract infection as claimed in claim 1 or 2, it comprises assay, discriminating etc., and it is characterized in that: the assay of method of quality control is an index with baicalin, chrysophanic acid, berberine; Discriminating is a reference substance with emodin, berberine hydrochloride, baicalin.
7, according to the method for quality control of the pharmaceutical preparation of YIQING of the described treatment upper respiratory tract infection of claim 6, it is characterized in that: assay is such: with methanol-0.2mol/L phosphate sodium dihydrogen buffer solution, regulate pH value to 2.7 with phosphoric acid, be mobile phase at 42: 58; The detection wavelength is 275nm; Precision takes by weighing the baicalin reference substance 12.5mg that is dried to constant weight at 105 ℃, puts in the 250ml measuring bottle, with the small amount of methanol dissolving, is diluted to scale with double distilled water, shakes up, and promptly gets the reference substance solution that contains baicalin 50 μ g among every 1ml; Get the content under this product content uniformity item, mixing, porphyrize, get about 0.75g, the accurate title, decide, and puts in the 100ml measuring bottle, adds methanol 10ml, supersound process 10 minutes, be diluted to scale with double distilled water, got this liquid centrifugal 10 minutes, the per minute rotating speed is 15000 commentaries on classics, divide and get supernatant, promptly get need testing solution; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure.
8, according to the method for quality control of the pharmaceutical preparation of YIQING of the described treatment upper respiratory tract infection of claim 6, it is characterized in that: discriminating is such:
(1) gets this product 8g, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put evaporate to dryness in the water-bath, residue adds water 10ml makes dissolving, add hydrochloric acid 1ml again, put in the water-bath and heated 30 minutes, immediately cooling, divide 2 extractions with chloroform 20ml, the combined chloroform extracting solution is concentrated into about 1ml, as need testing solution; Other gets the emodin reference substance, and chlorination is copied into the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 10 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, upper solution with petroleum ether-Ethyl formates of 60～90 ℃-formic acid=15: 5: 1 is developing solvent, launch, take out, dry, it is smoked clear to the speckle colour developing to put in the ammonia steam.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical punctation;
(2) get this product 8g, add methanol 50ml, 4～6 of dripping hydrochloric acid, jolting 20 minutes filters, and filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography test, draw each 10 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 ethyl acetate-butanone-formic acid-water=10: 6: 1: 1 was developing solvent, launches, and takes out, dry, spray is with 2% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical aeruginous speckle;
(3) get this product 8g, add methanol 50ml, flooded 2 hours, and jolting constantly, filtering, filtrate is put and is concentrated into about 1ml in the water-bath, as need testing solution.Other gets the berberine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to thin layer chromatography test, draw each 10 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 ethyl acetate-butanone-formic acid-water=10: 6: 1: 1 was developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical yellow fluorescence speckle.
Priority Applications (2)
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| CN 200510049767 CN1698757A (en) | 2005-05-09 | 2005-05-09 | Pharmaceutical preparation for treating upper respiratory tract infection and its preparation process and quality control method |
| CN2006102004002A CN1876039B (en) | 2005-05-09 | 2006-04-26 | Detection method of pharmaceutical composition for treating upper respiratory tract infection |
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| CN 200510049767 CN1698757A (en) | 2005-05-09 | 2005-05-09 | Pharmaceutical preparation for treating upper respiratory tract infection and its preparation process and quality control method |
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| CN101167829B (en) * | 2007-11-07 | 2010-10-13 | 胡团敏 | Traditional Chinese medicinal composition and enema for treating chronic colitis and preparation method thereof |
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| CN102631430A (en) * | 2012-04-19 | 2012-08-15 | 上海中医药大学 | Traditional Chinese medicine composition for resisting hepatic fibrosis, as well as preparation method and application thereof |
| CN103575841A (en) * | 2012-07-23 | 2014-02-12 | 洛阳惠中兽药有限公司 | Quality control method for Qiqing toxin-removing particles |
| CN110772566A (en) * | 2019-11-07 | 2020-02-11 | 辽宁康博士制药有限公司 | Traditional Chinese medicine composition for clearing heat and purging fire and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101167829B (en) * | 2007-11-07 | 2010-10-13 | 胡团敏 | Traditional Chinese medicinal composition and enema for treating chronic colitis and preparation method thereof |
| CN102552478A (en) * | 2010-12-16 | 2012-07-11 | 贵州万胜药业有限责任公司 | Quality detection method of Nine Ingredient Hemorrhoid Capsules |
| CN102631430A (en) * | 2012-04-19 | 2012-08-15 | 上海中医药大学 | Traditional Chinese medicine composition for resisting hepatic fibrosis, as well as preparation method and application thereof |
| CN102631430B (en) * | 2012-04-19 | 2013-11-13 | 上海中医药大学 | Traditional Chinese medicine composition for resisting hepatic fibrosis, as well as preparation method and application thereof |
| CN103575841A (en) * | 2012-07-23 | 2014-02-12 | 洛阳惠中兽药有限公司 | Quality control method for Qiqing toxin-removing particles |
| CN103575841B (en) * | 2012-07-23 | 2016-02-03 | 洛阳惠中兽药有限公司 | Seven relieve internal heat clearly granule content detection method |
| CN110772566A (en) * | 2019-11-07 | 2020-02-11 | 辽宁康博士制药有限公司 | Traditional Chinese medicine composition for clearing heat and purging fire and preparation method thereof |
| CN112587581A (en) * | 2020-10-23 | 2021-04-02 | 郑州大学第一附属医院 | Traditional Chinese medicine composition and application and preparation method thereof |
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