CN100478004C - Chinese medicinal composistion for treating common cold, its preparation method and quality control method - Google Patents
Chinese medicinal composistion for treating common cold, its preparation method and quality control method Download PDFInfo
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- CN100478004C CN100478004C CNB2005101323909A CN200510132390A CN100478004C CN 100478004 C CN100478004 C CN 100478004C CN B2005101323909 A CNB2005101323909 A CN B2005101323909A CN 200510132390 A CN200510132390 A CN 200510132390A CN 100478004 C CN100478004 C CN 100478004C
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Abstract
A Chinese medicine for treating cold is prepared from 5 Chinese-medicinal materials including bupleurum root, scutellaria root, isatis root, cyrtomium rhizome, etc. Its preparing process and quality control method are also disclosed.
Description
Technical field:
The present invention relates to a kind of medicine for the treatment of flu, particularly the Chinese medicine made of Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae.
Background technology:
Flu is global modal multiple disease, and the someone adds up the annual average flu of adult 3-4 time, and the child then reaches more than 6 times, 36% of worker's sick leave, and 67% of student's sick leave is due to flu.Flu has very big harm to anemia of pregnant woman, old man and child healthy, World Health Organization's statistics, and the people who dies from flu every year has at least more than 2,000,000 people.1918 in the world, nineteen fifty-seven and nineteen sixty-eight have been broken out large-scale influenza epidemic situation 3 times in the whole world, seized tens of millions of people's life.Cold virus can be propagated to healthy people by number of ways such as staff, air, dust contacts; The pollution of town and country air in recent years makes that Susceptible population is corresponding to increase, and also is to cause one of the factor that increases of catching a cold.Therefore active prevention and treatment flu are extremely important.The research and development of anti-cold medicine is in the ascendant in countries in the world.
Flu is many because of experiencing ailment said due to cold or exposure or touching when emitting due to the row virus.Common symptom: heating, nasal obstruction, watery nasal discharge, headache, cough, general malaise etc.The Chinese and western drugs of treatment flu is comparatively various, and pays attention to heat-clearing and toxic substances removing, inhibiting bacteria and diminishing inflammation, antivirus action more, the treatment flu is had certain effect, but belong to symptomatic treatment more, and for cold virus itself, still lack ideal effect.Its Chinese medicine and western medicine is used treatment flu such as antiviral, antibiotics, antiallergic, antihistamine always, and the symptomatic treatment of cold virus is the most extensive with antipyretic-antalgic agent use, contains salicylic acid, as aspirin more; The acetophenone amine is as acetaminophen; Pyrazolone is as aminophenazone etc.As compound recipe patent medicine have immediate effect cold capsule, contac, compound paracetamol and zinc gluconate tablets, paracetamol etc.Its common feature is a symptomatic treatment, and refrigeration function is very fast, and improves symptoms such as heating, headache, nasal obstruction, but finally still will lean on the spontaneous recovery of human autoimmune power.Such medicine has limited its scope of application owing to there are untoward reaction in various degree such as irritated, sleepy.The appearance of influenza vaccines, the treatment for this disease once provides a powerful mean, but because the variability of virus makes the application of vaccine increase difficulty.By contrast, the advantage of treatments such as Chinese medicine such as SHUANGHUANLIAN series, Radix Isatidis granule, the clear granule of flu flu is admitted that by common people removing curative effect can be outer, and its basic reason is at the different causes of disease, dialectical executing controlled, pay attention to patient's intrinsic resistance adjustment, the incomparable advantage of Western medicine is arranged.
The traditional Chinese medical science thinks that the main diseases of flu is because of being to experience ailment said due to cold or exposure." wind being the primary exopathogen ", wind are first of six gas, and among flowing in 4 o'clock, thereby the disease of diseases caused by exogenous pathogenic factor is based on wind.And ailment said due to cold or exposure invasion and attack human body is often non-ly hurted sb.'s feelings separately, many and other pathogen, or the time row virus, it is pathogenic to be harmonious, as holds under the arm to tremble with fear and form the card of wind and cold.Disease sees that aversion to cold is heavy, and heating is light, and is lossless, nasal obstruction, watery nasal discharge, the disease of systemic pain, thin white fur of tongue, floating pulse or floating tight; As hold the card that heat forms wind heat under the arm.Disease is seen the heating micro evil wind, watery nasal discharge, sneeze, nasal obstruction, sweating xerostomia, headache, pharyngalgia, the thick Huang of cough expectorant, tongue fur BOHUANG, floating and rapid pulse.
In recent years, along with going deep into of clinical research, occurred the Chinese medicine preparation of a lot of treatments flu on the market, but existing medicine belongs to a bit and cure the symptoms, not the disease, some uses expensive composition, and some interrupts use because uncertain therapeutic efficacy is cut in application process.
In view of this, the inventor develop a kind of taking convenience, effect steadily, determined curative effect, dosage form is stable, quality controllable and the treatment that has no side effect is caught a cold Chinese medicine medicine, to satisfy the demand of extensive patients.
The inventor by with Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae in conjunction with prescription, prepare successfully a kind of medicine that is used for the treatment of flu, overcome the defective of prior art, obtained beyond thought effect.
The present invention also provides preparation method, method of quality control, makes this drug manufacture standardization, reaches determined curative effect, steady quality, the advanced reasonably purpose of technology.
Summary of the invention:
The invention provides a kind of medicine for the treatment of flu, this medicine is formed through processing and preparing by bupleurum Chinese, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae.
Medicine of the present invention, its proportion of raw materials and weight portion are composed as follows:
Radix Bupleuri 50-450 part, Radix Scutellariae 50-460 part, Radix Helicteris 70-600 part, Radix Isatidis 50-500 part, Rhizoma Osmundae 50-500 part.
Preferably:
Radix Bupleuri 132-450 part, Radix Scutellariae 132-460 part, Radix Helicteris 198-600 part, Radix Isatidis 132-500 part, Rhizoma Osmundae 132-500 part.
Most preferably: 264.5 parts of Radix Bupleuri, 264.5 parts of Radix Scutellariaes, 396.7 parts of Radix Helicteriss, 264.5 parts of Radix Isatidis, 264.5 parts of Rhizoma Osmundae.
In more than forming, the weight of medicine is calculated with crude drug, with weight portion as proportioning, when producing, can proportionally increase or reduce, as large-scale production can be unit with the kilogram, or is unit with the ton, and small-scale production can be a unit with gram or milligram also, weight can increase or reduce, but the constant rate of the raw medicinal herbs weight proportion between each composition.
The ratio of above weight proportion obtains through science screening, for especial patient, and as serious symptom or light disease, fat or modest patient, the proportioning of the amount of can corresponding adjustment forming increases or reduces being no more than 100%, and drug effect is constant.
Raw material of Chinese medicine in more than forming can be replaced with the suitable Chinese medicine with identical property of medicine, and its drug effect of the Chinese medicine preparation after the replacement is constant.
Above weight portion calculates with gram as if every part, through can be made into 1000 doses of pharmaceutical preparatioies after the processing.Pharmaceutical preparation of the present invention is meant for 1000 doses, the final drug preparation of making, as make 1000 of capsule preparations, 1000 in tablet, granule 1000 grams, oral liquid 1000ml, 1000 of injections or 1000ml etc.
Chinese medicine preparation of the present invention is by the raw material of Chinese medicine of above-mentioned prescription being processed through extraction or other modes, being made pharmaceutically active substance, subsequently, with this material is raw material, adds the medicine acceptable carrier when needing, and makes preparation of the present invention according to the routine techniques of galenic pharmacy.Described active substance can obtain by the method that is selected from following mode, as: by pulverize, squeeze, calcine, grind, sieve, percolation, extraction, water are carried, alcohol extraction, ester are carried, methods such as ketone is carried, chromatography obtain, these active substances can be the material of extractum form, can be that dry extract also can be a fluid extract, make different concentration according to the different needs decision of preparation.
Pharmaceutical preparation of the present invention, the pharmaceutical dosage forms of unit dose preferably, can make any pharmaceutically useful dosage form when making pharmaceutical preparation, these dosage forms are selected from: granule, tablet (dispersible tablet, oral cavity disintegration tablet, enteric coatel tablets, the abnormity sheet, effervescent tablet, slow releasing tablet, double-layer tablet, multilayer tablet etc.), pill, powder, injection, powder, injectable powder, capsule (contains soft capsule, hard capsule, enteric coated capsule etc.), oral liquid, syrup, drop pill, unguentum, mixture, buccal tablet, membrane, Emulsion, nasal drop, aerosol, spray, microcapsule, suppository, aerosol, the sustained-release and controlled release preparation, any acceptable dosage form on the pharmaceuticss such as paster.Preferably oral formulations form, most preferably granule.
Medicine of the present invention, its pharmaceutically active substance preferably prepares through following method: get Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae five tastes medical material, Radix Scutellariae wherein, fragmentation adds the decocting that 4-12 doubly measures and boils 1-5 time, each 0.5-3 hour, filter, merging filtrate, being concentrated into relative density is 1.02～1.40 (40-90 ℃), the acidic liquid that adds 0.1-10mol/1 transfers pH value to 0.5-3.0,60-90 ℃ of insulation 0.5-3 hour left standstill and put coldly, filters, precipitation adds the distilled water that 2-6 doubly measures, regulate pH value to 5.0-7.0 with the 10%-40% alkaline solution, add 80-95% ethanol and make and contain the alcohol amount and be 35-70%, stir evenly, left standstill 4-24 hour, filter, filtrate is regulated pH value to 0.5～3.0 with the acid solution of 0.5-10mol/l, and 50-80 ℃ is incubated 1-4 hour, centrifugal, precipitation is 3.0～7.0 with an amount of distilled water wash to PH, and is centrifugal, drying, pulverize, standby; All the other four Chinese medicine materials, add the decocting that 4-12 doubly measures and boil 1-4 time, each 0.5-3 hour, filter, merging filtrate, being concentrated into relative density is 1.05～1.40 (40-90 ℃), adds 80-95% ethanol to containing alcohol amount 45-70%, stirs evenly, left standstill 12-48 hour, get supernatant, reclaim ethanol, and be concentrated into the extractum that relative density is 1.10～1.35 (50-75 ℃).
The acid solution that uses in the method for making can be sulphuric acid, hydrochloric acid, and alkaline solution can be NaOH, NaHCO
3, Na
2CO
3, KOH etc.
Preferred manufacturing procedure:
Get Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae five tastes medical material, Radix Scutellariae wherein, fragmentation, the decocting that adds 8 times of amounts boils 3 times, each 1 hour, filters, merging filtrate, being concentrated into relative density is 1.09～1.11 (65 ℃), the hydrochloric acid that adds 2mol/l is transferred pH value to 1.0～2.0,80 ℃ are incubated 1 hour, leave standstill and put coldly, filter, precipitation adds the distilled water of 4 times of amounts, stir, regulate pH value to 7.0 with 20%NaOH solution, add 85% ethanol and make that to contain the alcohol amount be 45%, stir evenly, left standstill 12 hours, filter, filtrate is regulated pH value to 1.0～2.0,70 ℃ insulation 2 hours with the hydrochloric acid of 2mol/l, centrifugal, precipitation is 4.0～5.0 with an amount of distilled water wash to PH, and is centrifugal, drying, pulverize, standby; All the other four flavors, the decocting that adds 8 times of amounts boils 2 times, each 1 hour, filters, merging filtrate, being concentrated into relative density is 1.17～1.20 (65 ℃), adds 85% ethanol to containing alcohol amount 60%, stirs evenly, left standstill 24 hours, get supernatant, reclaim ethanol, and be concentrated into the extractum that relative density is 1.25～1.28 (65 ℃).
Pharmaceutical preparation of the present invention can add some medicine acceptable carriers as required, can adopt the galenic pharmacy routine techniques to prepare this pharmaceutical preparation, as pharmaceutically active substance is mixed with the medicine acceptable carrier.Described medicine acceptable carrier is selected from: mannitol, sorbitol, sorbic acid or potassium salt, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin A, vitamin C, vitamin E, vitamin D, azone, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, aspartame, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, alginate, gelatin, polyvinylpyrrolidone, glycerol, propylene glycol, ethanol, soil temperature 60-80, span-80, Cera Flava, lanoline, liquid paraffin, hexadecanol, gallate ester, agar, triethanolamine, basic amino acid, carbamide, allantoin, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, the phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.
Pharmaceutical preparation of the present invention is determined usage and dosage according to patient's situation in use.
Chinese medicine preparation of the present invention, when making medicament, the medicament of unit dose can contain pharmaceutically active substance 0.1-1000mg of the present invention, and all the other are pharmaceutically acceptable carrier.Pharmaceutically acceptable carrier can be the 0.1-99.9% of total formulation weight amount by weight.
The most preferred prescription of the present invention is listed in the embodiment of the invention.
We establish for anemopyretic cold, and with relieving the exterior syndrome with drugs of pungent in flavor and cool in nature, heat-clearing and toxic substances removing is a method.Radix Bupleuri in the side, bitter in the mouth is slightly cold.Return liver, gallbladder meridian.The merit that having induces sweat brings down a fever.This product hardship can be let out, and be slightly cold to bring down a fever, and its light weight liter is diffusing, brings down a fever so be good at eliminating evil inducing sweat.Be usually used in the heating of diseases caused by exogenous pathogenic factor exterior syndrome and be monarch drug.Radix Scutellariae, the nature and flavor hardship, cold.Return lung, gallbladder, spleen, stomach, large intestine, small intestine meridian.The merit that heat-clearing and toxic substances removing is arranged.This product master goes into lung meridian, can the hypocatharsis lung-fire and part of the body cavity above the diaphragm housing the heart and lungs excess-heat, so the yellow thick disease of cough due to lung-heat's expectorant due to the also kind heresy of controlling wind heat is covered heat and is gone then that expectorant removes.Radix Helicteris, the nature and flavor hardship, cold.GUIXIN, lung meridian.The heat clearing away of inducing sweat is arranged, subduing swelling and detoxicating, clearing throat, the merit of expelling phlegm for arresting cough.Be usually used in cold, fever, headache, thirsty, diseases such as cough with copious phlegm." Nanning City's medicine will " meaning: " eruptive disease is controlled in the heat clearing away of inducing sweat, hot flu, skin infection ".Radix Scutellariae, Radix Helicteris share, and to strengthen the monarch drug relieving the exterior syndrome with drugs of pungent in flavor and cool in nature, the merit of heat-clearing and toxic substances removing is the ministerial drug in the side altogether.Radix Isatidis, hardship, cold.GUIXIN, stomach warp.Heat-clearing and toxic substances removing is arranged, removing heat from blood, the merit of sore-throat relieving.This product bitter cold is good at removing summer-heat excess-heat fire-toxin, the merit of the heat-clearing and toxic substances removing that is similar to Folium Isatidis is arranged, and more be good at the resolving toxin and disinhibiting the throat eliminating stagnation.So be usually used in treating affection due to external wind and heat or epidemic febrile disease from the beginning of diseases such as fever and headache, pharyngalgia.Rhizoma Osmundae, hardship, cold.The merit that heat-clearing and toxic substances removing is arranged.This product is bitter cool, and excess-heat that can the clearing heat in QI system branch can be separated the pyretic toxicity of blood system again, the card due to all warm heresies all available it, be usually used in the card of anemopyretic cold.Radix Isatidis, Rhizoma Osmundae 5 usefulness help the heat clearing away of inducing sweat of all medicines of the monarch and his subjects, resolving toxin and disinhibiting the throat, the effect of eliminating phlegm and stopping cough from different Fang Mianzuo.Be the adjuvant drug in the side altogether.
More than all medicines share, play relieving the exterior syndrome with drugs of pungent in flavor and cool in nature altogether, the merit of heat-clearing and toxic substances removing.Become relieving the exterior syndrome with drugs of pungent in flavor and cool in nature altogether, the agent of heat-clearing and toxic substances removing is used for flu.
Used medical material Radix Bupleuri, Radix Scutellariae, Radix Isatidis are in that " record in the Chinese pharmacopoeia (version in 20005), Radix Helicteris, Rhizoma Osmundae are recorded in " Guangxi medical material standard " (nineteen ninety version).
The present invention also provides the method for quality control of Chinese medicine preparation of the present invention, and this method comprises:
A carries out [discriminating] to the composition in the preparation,
B carries out [inspection] to preparation,
C carries out [assay] to effective ingredient in the preparation.
Wherein said to the composition in the preparation is carried out [discriminating], step is as follows:
Granule 10g of the present invention is got in discriminating (1), and porphyrize adds methanol 30-70ml, water-bath reflux, extract, 30-90 minute filters the filtrate evaporate to dryness, residue adds ammonia solution 15-45ml makes dissolving, extracts 2 times with water saturated n-butyl alcohol jolting, each 20-40ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add methanol 10-30ml makes dissolving, is added on the neutral alumina post of having handled well, with methanol 10-30ml eluting, eluent is concentrated into 1-4ml as need testing solution.Other gets Radix Bupleuri control medicinal material 1-3g, add water 20-150ml and decoct extraction 0.5-3.0 hour, filter, the n-butyl alcohol jolting that filtrate water is saturated is extracted 2 times, each 20-40ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add methanol 10-30ml makes dissolving, is added on the neutral alumina post of having handled well, with methanol 10-30ml eluting, eluent is concentrated into 1-4ml medical material solution in contrast.With reference to " the thin layer chromatography test of an appendix VI of Chinese pharmacopoeia version in 2005 B regulation, draw each 5-120 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 chloroform-methanol-water (3: 1: 0.1) is developing solvent, launch, take out, dry, spray is with the 20-60% sulfuric acid solution of 2% paradime thylaminobenzaldehyde, 60～70 ℃ of air cookings are clear to the speckle colour developing, put inspection under the daylight lamp, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
(2) get granule 1-5g of the present invention, add Diluted Alcohol 5-25ml, supersound process 1-3 minute, filter, filtrate is as need testing solution.Other gets the arginine reference substance, adds Diluted Alcohol and makes the solution that every 1ml contains 0.1-2.0mg, in contrast product solution.According to " the thin layer chromatography test of an appendix VI of Chinese pharmacopoeia version in 2005 B regulation, draw each 2-10 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, be developing solvent with n-butyl alcohol-glacial acetic acid-water (15: 5: 5), launch, take out, hot blast drying, spray is with ninhydrin solution, it is clear to be heated to speckle colour developing at 100-120 ℃, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Described preparation is carried out [inspection], step is as follows:
Inspection should meet every regulation relevant under the granule item (" appendix IC of Chinese pharmacopoeia version in 2005).
Described effective ingredient in the preparation is carried out [assay], step is as follows:
Assay
Measure according to high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia version in 2005 D).Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Methanol-water-phosphoric acid (50: 50: 0.2) is a mobile phase; The detection wavelength is 277nm.Number of theoretical plate calculates by the baicalin peak should be not less than 3000.
The preparation precision of reference substance solution takes by weighing at 4 hours baicalin reference substance of 60 ℃ of drying under reduced pressure an amount of, adds methanol and makes the solution that every 1ml contains 50-150 μ g, promptly.
This product under the content uniformity item is got in the preparation of need testing solution, and porphyrize is got 0.5-2.0g, the accurate title, decide, and the accurate 50-85% ethanol 100ml that adds claims to decide weight, supersound process 15-45 minute, put coldly, claim to decide weight again, supply the weight that subtracts mistake with 70% ethanol, shake up, filter, get subsequent filtrate, 0.3-1.0m the filter membrane pressurization filters, 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.
This product contains Radix Scutellariae with baicalin (C for every bag
21H
18O
11) meter, must not be less than 50mg.
The present invention is that the purposes, particularly preparation in the preparation treatment cold medicine treated the purposes in the anemopyretic cold medicine, and described disease disease is seen heating, micro evil wind, and nasal obstruction, watery nasal discharge, sneeze, the sweating xerostomia, headache, pharyngalgia, cough expectorant Huang is thick, tongue fur BOHUANG, floating and rapid pulse etc.
Following data by experiment illustrate beneficial effect of the present invention:
Main pharmacodynamics research
The effect of 1 resisting pathogenic microbes
1.1 interior resisting virus test
(1). adopt first
1Type influenza virus FM
1The strain infecting mouse is an animal model, with lung index and lung index suppression ratio is that evaluation index is observed the effect of the dried cream resisiting influenza virus of the present invention, with crude drug 12.15,4.86,1.62g/kg dosage (be respectively clinical plan consumption 30,12,4 times) gastric infusion, once a day, continuous 4 days.The result shows the mouse lung pathological changes (P＜0.05, P＜0.01) that the dried cream of the present invention of three dosage all can obviously suppress influenza virus and causes;
(2). adopt first
1Type influenza virus FM
1The strain infecting mouse is an animal model; observe the dried cream of the present invention to the protection of virus infected mice death with prolong disease Mus vital action; with crude drug 12.15,4.86,1.62g/kg dosage (be respectively clinical plan consumption 30,12,4 times) gastric infusion, once a day, continuous 12 days.The result shows that the dried cream of the present invention of three dosage all can obviously prolong the life span of infecting mouse (P＜0.05, P＜0.01), has sure dead protective effect.
1.2 extracorporeal antivirus effect test
External preventing respiratory viruses test shows that the dried cream of the present invention can suppress rhinovirus 14 types, influenza A virus FM under non-toxic concn
1, respiratory syncytial virus (RSV long strain), parainfluenza virus and adenovirus type VII cytopathic effect, inhibition concentration is respectively crude drug 2.83mg/ml, 4.05mg/ml, 1.30mg/ml, 0.81mg/ml, 16.2mg/ml.
1.3 in-vitro antibacterial test
This test select for use 5 kinds representational, cause that particularly the encountered pathogenic bacteria of respiratory infections and conditioned pathogen are to detect the antibacterial action of the dried cream of the present invention.The result shows, this preparation is stronger to staphylococcus aureus, beta hemolytic streptococcus, colibacillary inhibitory action, and their minimal inhibitory concentration (MIC) is respectively crude drug 0.8mg/ml, 1.6mg/ml, 6.4mg/ml.
2. antiinflammatory, analgesic activity
(1). utilize the experiment of mouse peritoneal capillary permeability to be animal antiinflammatory model, the AZO-blue amount of dye of oozing out with intraperitoneal is an index, estimates the antiinflammatory action of the dried cream of the present invention.With crude drug 12.15,4.86,1.62g/kg dosage (be respectively clinical plan consumption 30,12,4 times) gastric infusion, once a day, continuous 4 days.The result shows that three dosage of the dried cream of the present invention all can obviously reduce animal pattern abdominal cavity capillary permeability (P＜0.01);
(2). observing the influence to rat paw edema due to the Ovum Gallus domesticus album, is the antiinflammatory action of the dried cream of index evaluation the present invention with the foot swelling percentage rate.With crude drug 6.07,2.43,0.81g/kg dosage (be respectively clinical plan consumption 15,6,2 times) gastric infusion, once a day, continuous 4 days.The result shows that three dosage of the dried cream of the present invention in the 0.5th, 2,4,6 hour all have antiinflammatory action behind albumen injection, with model group comparing difference remarkable (P＜0.05, P＜0.01); Only there were height, middle dosage group to show antiinflammatory action (P＜0.01) in 1 hour after the administration;
(3). utilize the acetic acid induced mice to turn round body experiment and be the animal pain model, turning round the body number of times with mice in 20 minutes is index, estimates the analgesic activity of the dried cream of the present invention.With crude drug 12.15,4.86,1.62g/kg dosage (be respectively clinical plan consumption 30,12,4 times) gastric infusion 1 time, the result shows in the dried cream of the present invention, low dosage has significant analgesia role (P＜0.01), and middle dosage analgesic activity is similar to the effect of sodium salicylate.
3. to immune effect
(1). observe influence,, estimate of the influence of the dried cream of the present invention humoral immune function to be index to mice serum hemolytic antibody generative capacity to the inductive circulating antibody level of chicken red blood cell.With crude drug 12.15,4.86,1.62g/kg dosage (be respectively clinical plan consumption 30,12,4 times) gastric infusion, once a day, continuous 7 days.The result shows that the dried cream height of the present invention, middle dosage group are to the mice sheep red blood cell inducing specific circulating antibody level effect of being significantly improved (P＜0.05, P＜0.01);
(2). observe influence to macrophage phagocytic function.Cleaning up index with carbon is that the dried cream of index evaluation the present invention is to Immune Effects with engulfing coefficient.With crude drug 12.15,4.86,1.62g/kg dosage (be respectively clinical plan consumption 30,12,4 times) gastric infusion, once a day, continuous 8 days.The result shows that three dosage of the dried cream of the present invention all can obviously improve and cleans up index (P＜0.05, P＜0.01); High dose group can also obviously improve the liver spleen and engulf coefficient (P＜0.01), shows that the dried cream of the present invention has obvious activation and potentiation to the reticuloendothelial system phagocytic function;
(3). observing the influence to the inductive mice delayed hypersensitivity of DNFB, is the influence of the dried cream of index evaluation the present invention to delayed hypersensitivity with left and right sides auricle method of double differences value.With crude drug 12.15,4.86,1.62g/kg dosage (be respectively clinical plan consumption 30,12,4 times) gastric infusion, once a day, continuous 9 days.The result shows that three dosage of the dried cream of the present invention are all to the super quick obvious suppression effect (P＜0.01) that has of the inductive mice delayed of DNFB;
Toxicological study
1. acute toxicity test
Get SPF level kunming mice, offer medicine to mouse stomach so that the dried cream crude drug of the present invention dried cream powder is disposable, maximum tolerated dose is crude drug 165.24g/kg (being equivalent to clinical plan 413 times with daily dose according to the weight), after the administration in 7 days the outward appearance of mice, activity, behavior, feed, drainage etc. show no obvious abnormalities, the no phenomena of mortality, the weight of mice situation is normal.
2 long term toxicity tests
Getting SPF level Wistar is that rat carries out long term toxicity test, the result shows, gavage the dried cream crude drug of the present invention 13 weeks of dried cream powder continuously for respectively rat by the dosage (clinical plan is with 120 times, 60 times, 30 times of daily dose) of crude drug 48g/kg, 24g/kg, 12g/kg, the PLT counting appears in the 48g/kg group, GLU content reduces, ALP activity, CK activity, index and spleen index, kidney index, ovary index, testis index increase (P＜0.05, P＜0.01); The PLT counting appears in the 24g/kg group, GLU content reduces, and ALP activity, index and spleen index, ovary index, testis index increase (P＜0.05, P＜0.01); The ALP activity appears in the 12g/kg group, the ovary index increases (P＜0.05, P＜0.01), but These parameters is still in normal range; After 2 weeks of drug withdrawal, the GLU content of each administration group, ALP activity, CK activity, index and spleen index, kidney index, ovary index, testis index all can be recovered, compare there was no significant difference with matched group, the PLT counting also has tangible recovery trend, shows that above-mentioned variation is reversible; Do not observe other tangible toxic reaction and delay toxic reaction; The pathological changes relevant with being subjected to the reagent thing do not found in the main organs histological examination.
It may be safe that result of the test prompting, the dried cream of the present invention are used consumption, approach, the course of treatment in accordance with regulations clinically, but should pay close attention to the PLT counting of blood, the variation of GLU content when clinical practice; Should avoid long-term heavy dose of use simultaneously.
The specific embodiment:
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1
Prescription:
Radix Bupleuri 264.5 grams, Radix Scutellariae 264.5 grams, Radix Helicteris 396.7 grams, Radix Isatidis 264.5 grams, Rhizoma Osmundae 264.5 grams.
Get Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae five tastes medical material, Radix Scutellariae wherein, fragmentation, the decocting that adds 8 times of amounts boils 3 times, each 1 hour, filters, merging filtrate, being concentrated into relative density is 1.09～1.11 (65 ℃), the hydrochloric acid that adds 2mol/l is transferred pH value to 1.0～2.0,80 ℃ are incubated 1 hour, leave standstill and put coldly, filter, precipitation adds the distilled water of 4 times of amounts, stir, regulate pH value to 7.0 with 20%NaOH solution, add 85% ethanol and make that to contain the alcohol amount be 45%, stir evenly, left standstill 12 hours, filter, filtrate is regulated pH value to 1.0～2.0,70 ℃ insulation 2 hours with the hydrochloric acid of 2mol/l, centrifugal, precipitation is 4.0～5.0 with an amount of distilled water wash to PH, and is centrifugal, drying, pulverize, standby; All the other four flavors, the decocting that adds 8 times of amounts boils 2 times, each 1 hour, filters, merging filtrate, being concentrated into relative density is 1.17～1.20 (65 ℃), adds 85% ethanol to containing alcohol amount 60%, stirs evenly, left standstill 24 hours, get supernatant, reclaim ethanol, and be concentrated into the extractum that relative density is 1.25～1.28 (65 ℃).
Embodiment 2
Prescription: Radix Bupleuri 50 grams, Radix Scutellariae 50 grams, Radix Helicteris 70 grams, Radix Isatidis 50 grams, Rhizoma Osmundae 50 grams.
Get Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae five tastes medical material, Radix Scutellariae wherein, fragmentation, the decocting that adds 8 times of amounts boils 3 times, each 1 hour, filters, merging filtrate, being concentrated into relative density is 1.09～1.11 (65 ℃), the hydrochloric acid that adds 2mol/l is transferred pH value to 1.0～2.0,80 ℃ are incubated 1 hour, leave standstill and put coldly, filter, precipitation adds the distilled water of 4 times of amounts, stir, regulate pH value to 7.0 with 20%NaOH solution, add 85% ethanol and make that to contain the alcohol amount be 45%, stir evenly, left standstill 12 hours, filter, filtrate is regulated pH value to 1.0～2.0,70 ℃ insulation 2 hours with the hydrochloric acid of 2mol/l, centrifugal, precipitation is 4.0～5.0 with an amount of distilled water wash to PH, and is centrifugal, drying, pulverize, standby; All the other four flavors, the decocting that adds 8 times of amounts boils 2 times, each 1 hour, filters, merging filtrate, being concentrated into relative density is 1.17～1.20 (65 ℃), adds 85% ethanol to containing alcohol amount 60%, stirs evenly, left standstill 24 hours, get supernatant, reclaim ethanol, and be concentrated into the extractum that relative density is 1.25～1.28 (65 ℃).
Embodiment 3
Prescription: Radix Bupleuri 450 grams, Radix Scutellariae 460 grams, Radix Helicteris 600 grams, Radix Isatidis 500 grams, Rhizoma Osmundae 500 grams.
Get Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae five tastes medical material, Radix Scutellariae wherein, fragmentation, the decocting that adds 8 times of amounts boils 3 times, each 1 hour, filters, merging filtrate, being concentrated into relative density is 1.09～1.11 (65 ℃), the hydrochloric acid that adds 2mol/l is transferred pH value to 1.0～2.0,80 ℃ are incubated 1 hour, leave standstill and put coldly, filter, precipitation adds the distilled water of 4 times of amounts, stir, regulate pH value to 7.0 with 20%NaOH solution, add 85% ethanol and make that to contain the alcohol amount be 45%, stir evenly, left standstill 12 hours, filter, filtrate is regulated pH value to 1.0～2.0,70 ℃ insulation 2 hours with the hydrochloric acid of 2mol/l, centrifugal, precipitation is 4.0～5.0 with an amount of distilled water wash to PH, and is centrifugal, drying, pulverize, standby; All the other four flavors, the decocting that adds 8 times of amounts boils 2 times, each 1 hour, filters, merging filtrate, being concentrated into relative density is 1.17～1.20 (65 ℃), adds 85% ethanol to containing alcohol amount 60%, stirs evenly, left standstill 24 hours, get supernatant, reclaim ethanol, and be concentrated into the extractum that relative density is 1.25～1.28 (65 ℃).
Embodiment 4
The preparation of tablet,
Get the extractum of embodiment 1, drying is pulverized, and adds starch, and mixing adds an amount of 95% ethanol moistening, granulates, and granulate adds Pulvis Talci, magnesium stearate, and tabletting, coating promptly get tablet.
Embodiment 5
The preparation of capsule,
Get the extractum of embodiment 1, drying is pulverized, and adds starch, and mixing adds an amount of 95% ethanol moistening, granulate, and granulate, promptly encapsulated.
Embodiment 6
The preparation of granule,
Get the extractum of embodiment 1, drying is pulverized, and adds starch, sucrose, and mixing adds an amount of 95% ethanol moistening, granulates, granulate, packing promptly gets granule.
Claims (8)
1, a kind of anti-cold medicine is characterized in that, makes with following Chinese medicinal raw materials:
Radix Bupleuri 50-450 part, Radix Scutellariae 50-460 part, Radix Helicteris 70-600 part, Radix Isatidis 50-500 part, Rhizoma Osmundae 50-500 part.
2, the medicine of claim 1 is characterized in that, makes with following Chinese medicinal raw materials:
Radix Bupleuri 132-450 part, Radix Scutellariae 132-460 part, Radix Helicteris 198-600 part, Radix Isatidis 132-500 part, Rhizoma Osmundae 132-500 part.
3, the medicine of claim 1 is characterized in that, makes with following Chinese medicinal raw materials:
264.5 parts of Radix Bupleuri, 264.5 parts of Radix Scutellariaes, 396.7 parts of Radix Helicteriss, 264.5 parts of Radix Isatidis, 264.5 parts of Rhizoma Osmundae.
4, each medicine of claim 1-3, it is characterized in that its dosage form is selected from: granule, tablet, pill, powder, injection, injectable powder, capsule, oral liquid, syrup, unguentum, mixture, membrane, Emulsion, nasal drop, aerosol, spray, microcapsule, suppository and paster.
5, the preparation method of each medicine of claim 1-3, it is characterized in that, Chinese medicinal raw materials is processed through extraction or other modes, make pharmaceutically active substance, subsequently, with this material is raw material, adds the medicine acceptable carrier when needing, and makes medicine according to the routine techniques of galenic pharmacy.
6, the preparation method of claim 5 is characterized in that, the process following steps:
Get Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae five tastes medical material, Radix Scutellariae wherein, fragmentation, add the decocting that 4-12 doubly measures and boil 1-5 time, each 0.5-3 hour, filter, merging filtrate, when being concentrated into relative density 40-90 ℃ is 1.02～1.40, and the acidic liquid that adds 0.1-10mol/l transfers pH value to 0.5-3.0, and 60-90 ℃ is incubated 0.5-3 hour, leave standstill put cold, filter, precipitation adds the distilled water that 2-6 doubly measures, and regulates pH value to 5.0-7.0 with the 10%-40% alkaline solution, adding 80-95% ethanol makes the alcohol amount of containing be 35-70%, stir evenly, left standstill 4-24 hour, filter, filtrate is regulated pH value to 0.5～3.0 with the acid solution of 0.5-10mol/l, 50-80 ℃ the insulation 1-4 hour, centrifugal, the precipitation with an amount of distilled water wash to PH be 3.0～7.0, centrifugal, drying is pulverized, and is standby; All the other four Chinese medicine materials, add the decocting that 4-12 doubly measures and boil 1-4 time, each 0.5-3 hour, filter, merging filtrate, when being concentrated into relative density 40-90 ℃ is 1.05～1.40, adds 80-95% ethanol to containing alcohol amount 45-70%, stirs evenly, left standstill 12-48 hour, get supernatant, reclaim ethanol, and be 1.10～1.35 extractum when being concentrated into relative density 50-75 ℃.
7, the preparation method of claim 5 is characterized in that, the process following steps:
Get Radix Bupleuri, Radix Scutellariae, Radix Helicteris, Radix Isatidis, Rhizoma Osmundae five tastes medical material, Radix Scutellariae wherein, fragmentation, the decocting that adds 8 times of amounts boils 3 times, each 1 hour, filters, merging filtrate is 1.09～1.11 when being concentrated into 65 ℃ of relative densities, and the hydrochloric acid that adds 2mol/l is transferred pH value to 1.0～2.0,80 ℃ are incubated 1 hour, leave standstill and put coldly, filter, precipitation adds the distilled water of 4 times of amounts, stir, regulate pH value to 7.0 with 20%NaOH solution, add 85% ethanol and make that to contain the alcohol amount be 45%, stir evenly, left standstill 12 hours, filter, filtrate is regulated pH value to 1.0～2.0,70 ℃ insulation 2 hours with the hydrochloric acid of 2mol/l, centrifugal, precipitation is 4.0～5.0 with an amount of distilled water wash to PH, and is centrifugal, drying, pulverize, standby; All the other four flavors, the decocting that adds 8 times of amounts boils 2 times, each 1 hour, filters, merging filtrate, when being concentrated into 65 ℃ of relative densities is 1.17～1.20, adds 85% ethanol to containing alcohol amount 60%, stirs evenly, left standstill 24 hours, get supernatant, reclaim ethanol, and be 1.25～1.28 extractum when being concentrated into 65 ℃ of relative densities.
8, the method for quality control of the medicine of claim 1 is characterized in that, may further comprise the steps:
A differentiates the composition in the preparation,
B checks preparation,
C carries out assay to effective ingredient in the preparation,
Wherein said composition in the preparation is differentiated that step is as follows:
(1) get granule 10g, porphyrize adds methanol 30-70ml, water-bath reflux, extract, 30-90 minute filters the filtrate evaporate to dryness, residue adds ammonia solution 15-45ml makes dissolving, extracts 2 times with water saturated n-butyl alcohol jolting, each 20-40ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add methanol 10-30ml makes dissolving, is added on the neutral alumina post of having handled well, with methanol 10-30ml eluting, eluent is concentrated into 1-4ml as need testing solution; Other gets Radix Bupleuri control medicinal material 1-3g, add water 20-150ml and decoct extraction 0.5-3.0 hour, filter, the n-butyl alcohol jolting that filtrate water is saturated is extracted 2 times, each 20-40ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add methanol 10-30ml makes dissolving, is added on the neutral alumina post of having handled well, with methanol 10-30ml eluting, eluent is concentrated into 1-4ml medical material solution in contrast, with reference to the thin layer chromatography test of an appendix VI of Chinese Pharmacopoeia version in 2005 B regulation, draws each 5-120 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 chloroform-methanol-water=3: 1: 0.1 was developing solvent, launched, and took out, dry, spray is with the 20-60% sulfuric acid solution of 2% paradime thylaminobenzaldehyde, and 60～70 ℃ of air cookings are clear to the speckle colour developing, put inspection under the daylight lamp, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(2) get granule 1-5g of the present invention, add Diluted Alcohol 5-25ml, supersound process 1-3 minute, filter, filtrate is as need testing solution, and other gets the arginine reference substance, adds Diluted Alcohol and makes the solution that every 1ml contains 0.1-2.0mg, in contrast product solution; Thin layer chromatography test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B regulation, draw each 2-10 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, be developing solvent with n-butyl alcohol-glacial acetic acid-water=15: 5: 5, launch, take out, hot blast drying, spray is with ninhydrin solution, it is clear to be heated to speckle colour developing at 100-120 ℃, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
Wherein saidly preparation is checked step is as follows:
Inspection is according to " an appendix I of Chinese pharmacopoeia version in 2005 C meets every regulation relevant under the granule item;
Wherein said effective ingredient in the preparation is carried out assay, step is as follows:
Measure according to an appendix VI of Chinese Pharmacopoeia version in 2005 D high performance liquid chromatography; Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Methanol-water-phosphoric acid=50: 50: 0.2 is a mobile phase; The detection wavelength is 277nm; Number of theoretical plate calculates by the baicalin peak should be not less than 3000;
The preparation precision of reference substance solution takes by weighing at 4 hours baicalin reference substance of 60 ℃ of drying under reduced pressure an amount of, adds methanol and makes the solution that every 1ml contains 50-150 μ g, promptly;
The granule under the content uniformity item is got in the preparation of need testing solution, and porphyrize is got 0.5-2.0g, the accurate title, decide, and the accurate 50-85% ethanol 100ml that adds claims to decide weight, supersound process 15-45 minute, put coldly, claim to decide weight again, supply the weight that subtracts mistake with 70% ethanol, shake up, filter, get subsequent filtrate, 0.3-1.0m the filter membrane pressurization filters, 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; Every bag 5.5 gram of granule contains Radix Scutellariae in baicalin, must not be less than 50mg.
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| 感冒的病因病机及其辨证分型. 乐鸣.实用中医内科杂志，第16卷第4期. 2002 * |
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Application publication date: 20060830 Assignee: Sanjin Group Hunan Sanjin Pharmaceutical Co., Ltd. Assignor: Sanjin Pharmaceutical Co., Ltd., Guilin Contract record no.: 2009450000075 Denomination of invention: Chinese medicinal composistion for treating common cold, its preparation method and quality control method Granted publication date: 20090415 License type: Exclusive License Record date: 20090925 |