Summary of the invention
The purpose of this invention is to provide pharmaceutical composition with prevention and treatment bird flu effect.
Another object of the present invention provides preparation of drug combination method of the present invention.
Another object of the present invention provides the application of pharmaceutical composition of the present invention in the medicine of preparation prevention or treatment bird flu.
Another object of the present invention provides the application of pharmaceutical composition of the present invention in the health product of preparation prevention or treatment bird flu.
In an embodiment of the invention, pharmaceutical composition with prevention and treatment bird flu effect comprises active component and/or pharmaceutically acceptable carrier, and wherein active component mainly contains following crude drug: Radix Isatidis 4.7wt.%-70.0wt.%, Fructus Forsythiae 2.3wt.%-39.7wt.%, Herba Pogostemonis 2.3wt.%-37.3wt.%, Rhizoma Anemarrhenae 1.4wt.%-28.0wt.% and other antipyretic and antidotal type Chinese medicine.
Above-mentioned antipyretic and antidotal type Chinese medicine is antipyretic and antidotal type Chinese medicine composition such as Rhizoma Phragmitis, Gypsum Fibrosum, Herba Andrographis, Herba Taraxaci, Indigo Naturalis, Caulis Sargentodoxae and Radix Glycyrrhizae.
The active component of aforementioned pharmaceutical compositions also can be made up of following crude drug: Radix Isatidis 4.7wt.%-70.0wt.%, Fructus Forsythiae 2.3wt.%-39.7wt.%, Herba Pogostemonis 2.3wt.%-37.3wt.%, Rhizoma Anemarrhenae 1.4wt.%-28.0wt.%,
This active ingredient in pharmaceutical preferably is made up of following crude drug: Radix Isatidis 14.0wt.%-46.7wt.%, Fructus Forsythiae 4.7wt.%-25.7wt.%, Herba Pogostemonis 1.4wt.%-28.0wt.%, Rhizoma Anemarrhenae 1.4wt.%-28.0wt.%.
In yet another embodiment of the present invention, pharmaceutical composition with prevention and treatment bird flu effect comprises active component and/or pharmaceutically acceptable carrier, and wherein active component mainly contains following crude drug: Radix Isatidis 4.7wt.%-46.7wt.%, Fructus Forsythiae 2.3wt.%-39.7wt.%, Gypsum Fibrosum 3.3wt.%-39.7wt.%, Rhizoma Phragmitis 2.8wt.%-42.0wt.%, Herba Pogostemonis 2.3wt.%-37.3wt.%, Rhizoma Anemarrhenae 1.4wt.%-28.0wt.% and other antipyretic and antidotal type Chinese medicine.
Above-mentioned antipyretic and antidotal type Chinese medicine is Rhizoma Acori Graminei, Radix Curcumae, Fructus Bruceae, Herba Andrographis, Herba Taraxaci, Herba Menthae, Radix Platycodonis and Radix Glycyrrhizae etc.
The active component of aforementioned pharmaceutical compositions also can be made up of following crude drug: Radix Isatidis 4.7wt.%-46.7wt.%, Fructus Forsythiae 2.3wt.%-39.7wt.%, Gypsum Fibrosum 3.3wt.%-39.7wt.%, Rhizoma Phragmitis 2.8wt.%-42.0wt.%, Herba Pogostemonis 2.3wt.%-37.3wt.%, Rhizoma Anemarrhenae 1.4wt.%-28.0wt.%.
This active ingredient in pharmaceutical preferably is made up of following crude drug:: Radix Isatidis 14.0wt.%-37.3wt.%, Fructus Forsythiae 4.7wt.%-25.7wt.%, Gypsum Fibrosum 3.3wt.%-25.7wt.%, Rhizoma Phragmitis 3.7wt.%-25.7wt.%, Rhizoma Anemarrhenae 3.7wt.%-14.0wt.%, Herba Pogostemonis 3.7wt.%-11.7wt.%.
In yet another embodiment of the present invention, pharmaceutical composition with prevention and treatment bird flu effect comprises active component and/or pharmaceutically acceptable carrier, and wherein active component is made up of following crude drug: Radix Isatidis 4.7wt.%-46.7wt.%, Fructus Forsythiae 2.3wt.%-39.7wt.%, Gypsum Fibrosum 3.3wt.%-39.7wt.%, Rhizoma Phragmitis 2.8wt.%-42.0wt.%, Radix Rehmanniae 3.3wt.%-37.3wt.%, Herba Pogostemonis 2.3wt.%-37.3wt.%, Rhizoma Acori Graminei 1.4wt.%-28.0wt.%, Radix Curcumae 1.4wt.%-28.0wt.%, Rhizoma Anemarrhenae 1.4wt.%-28.0wt.%.
The composition of the crude drug in the active component of aforementioned pharmaceutical compositions is preferably: Radix Isatidis 14.0wt.%-37.3wt.%, Fructus Forsythiae 4.7wt.%-25.7wt.%, Gypsum Fibrosum 3.3wt.%-25.7wt.%, Rhizoma Phragmitis 3.7wt.%-25.7wt.%, Radix Rehmanniae 3.7wt.%-14.0wt.%, Herba Pogostemonis 3.7wt.%-11.7wt.%, Rhizoma Acori Graminei 3.7wt.%-14.0wt.%, Radix Curcumae 3.7wt.%-14.0wt.%, Rhizoma Anemarrhenae 3.7wt.%-14.0wt.%.
More preferably: Radix Isatidis (RADIX ISATIDIS) 30.1wt.%, Fructus Forsythiae (FRUCTUSFORSYTHIAE) 10.8wt.%, Gypsum Fibrosum (GYPSUM FIBROSUM) 13.4wt.%, the Rhizoma Anemarrhenae (RHIZOMA ANEMARRHENAE) 5.8wt.%, Rhizoma Phragmitis (RHIZOMAPHRAGMITIS) 14.2wt.%, Radix Rehmanniae (RADIX REHMANNIAE) 7.5wt.%, Herba Pogostemonis (HERBA POGOSTEMONIS) 6.6wt.%, Rhizoma Acori Graminei (RHIZOMAACORI TATARINOWII) 5.8wt.%, Radix Curcumae (RADIX CURCUMAE) 5.8wt.%.
Pharmaceutical composition of the present invention can adopt the conventional method of Chinese medicine preparation to be prepared into any regular dosage form.For example can be with crude drug pulverize of the present invention, mix homogeneously is made powder and is taken after mixing it with water; Also can be with crude drug decocting of the present invention, condensed water decocting liquid then.But, better bring into play drug effect in order to make each crude drug of the present invention, preferably the Rhizoma Anemarrhenae in the crude drug is carried out special extraction, as ethanol extraction.But these can not be used to limit protection scope of the present invention.
Preferably, the preparation of drug combination method be made up of Radix Isatidis, Fructus Forsythiae, Herba Pogostemonis and the Rhizoma Anemarrhenae etc. of the present invention may further comprise the steps:
Get above 4 flavor recipe quantities.At first the Rhizoma Anemarrhenae is broken into coarse powder, adds 80%~95% alcohol heating reflux and extract 3 times, each 3 hours, filter, decompression filtrate recycling ethanol also concentrates, and obtaining relative density is the clear paste of 1.10 (80 ℃ of mensuration).Radix Isatidis etc. 3 flavor decocts with water three times (collecting volatile oil simultaneously), and 1 hour for the first time, the 2nd, 3 time each 0.5 hour, to filter, filtrate concentrates, and obtains relative density and be 1.16 clear paste.Get above-mentioned two kinds of clear paste, add lactose, sodium cyclamate is an amount of, makes lactose type granule, or add dextrin, sodium cyclamate is an amount of, makes sugar type granules, the volatile oil and the flavorant that add above-mentioned collection again are an amount of, mixing, promptly; Or get above-mentioned two kinds of clear paste mix homogeneously, and concentrate, obtain relative density and be 1.30 clear paste, qinghuo reagent, it is an amount of to add cane sugar powder, makes granule, drying, the volatile oil and the flavorant that add above-mentioned collection are an amount of, and mixing is made the sugar-containing type granule.
Crude drug in the above-mentioned preparation method can also make up with Rhizoma Phragmitis and Gypsum Fibrosum, perhaps further makes up Herba Andrographis, Herba Taraxaci, Indigo Naturalis, Caulis Sargentodoxae or Radix Glycyrrhizae, and its preparation method is:
Get recipe quantities such as above Radix Isatidis, Fructus Forsythiae, Herba Pogostemonis, the Rhizoma Anemarrhenae, Rhizoma Phragmitis and Gypsum Fibrosum.At first the Rhizoma Anemarrhenae is broken into coarse powder, adds 80%~95% alcohol heating reflux and extract 3 times, each 3 hours, filter, decompression filtrate recycling ethanol also concentrates, and obtaining relative density is the clear paste of 1.10 (80 ℃ of mensuration).All the other crude drug such as Radix Isatidis decoct with water three times (collecting volatile oil simultaneously), and 1 hour for the first time, the 2nd, 3 time each 0.5 hour, to filter, filtrate concentrates, and obtains relative density and be 1.16 clear paste.Get above-mentioned two kinds of clear paste, add lactose, sodium cyclamate is an amount of, makes lactose type granule, or add dextrin, sodium cyclamate is an amount of, makes sugar type granules, the volatile oil and the flavorant that add above-mentioned collection again are an amount of, mixing, promptly; Or get above-mentioned two kinds of clear paste mix homogeneously, and concentrate, obtain relative density and be 1.30 clear paste, qinghuo reagent, it is an amount of to add cane sugar powder, makes granule, drying, the volatile oil and the flavorant that add above-mentioned collection are an amount of, and mixing is made the sugar-containing type granule.
Crude drug in the above-mentioned preparation method can also with the combination of Rhizoma Acori Graminei, Radix Curcumae, perhaps further combination, Fructus Bruceae, Herba Andrographis, Herba Taraxaci, Herba Menthae, Radix Platycodonis or Radix Glycyrrhizae, its preparation method is:
Get recipe quantities such as above Radix Isatidis, Fructus Forsythiae, Herba Pogostemonis, the Rhizoma Anemarrhenae, Rhizoma Phragmitis, Gypsum Fibrosum, Rhizoma Acori Graminei and Radix Curcumae.At first the Rhizoma Anemarrhenae is broken into coarse powder, adds 80%~95% alcohol heating reflux and extract 3 times, each 3 hours, filter, decompression filtrate recycling ethanol also concentrates, and obtaining relative density is the clear paste of 1.10 (80 ℃ of mensuration).Radix Isatidis etc. decoct with water (collecting volatile oil simultaneously) three times, and 1 hour for the first time, the 2nd, 3 time each 0.5 hour, to filter, filtrate concentrates, and obtains relative density and be 1.16 clear paste.Get above-mentioned two kinds of clear paste, add lactose, sodium cyclamate is an amount of, makes lactose type granule, or add dextrin, sodium cyclamate is an amount of, makes sugar type granules, the volatile oil and the flavorant that add above-mentioned collection again are an amount of, mixing, promptly; Or get above-mentioned two kinds of clear paste mix homogeneously, and concentrate, obtain relative density and be 1.30 clear paste, qinghuo reagent, it is an amount of to add cane sugar powder, makes granule, drying, the volatile oil and the flavorant that add above-mentioned collection are an amount of, and mixing is made the sugar-containing type granule.
The preparation of drug combination method that the present invention is made up of Radix Isatidis, Fructus Forsythiae, Gypsum Fibrosum, Rhizoma Phragmitis, Radix Rehmanniae, Herba Pogostemonis, Rhizoma Acori Graminei, Radix Curcumae and the Rhizoma Anemarrhenae may further comprise the steps:
Get above nine flavor recipe quantities.At first Rhizoma Anemarrhenae powder is broken into coarse powder, adds 80%~95% alcohol heating reflux and extract 3 times, each 3 hours, filter, decompression filtrate recycling ethanol also concentrates, and obtaining relative density is the clear paste of 1.10 (50 ℃ of mensuration).8 flavors such as Radix Isatidis decoct with water three times (collecting volatile oil simultaneously), and 1 hour for the first time, the 2nd, 3 time each 0.5 hour, to filter, filtrate concentrates, and obtaining relative density is the clear paste of 1.16 (50 ℃ of mensuration).Get above-mentioned two kinds of clear paste, add lactose, sodium cyclamate is an amount of, makes lactose type granule, or add dextrin, sodium cyclamate is an amount of, makes sugar type granules, the volatile oil and the flavorant that add above-mentioned collection again are an amount of, mixing, promptly; Or get above-mentioned two kinds of clear paste mix homogeneously, and concentrate, obtaining relative density is the clear paste of 1.28~1.30 (55-60 ℃), qinghuo reagent, it is an amount of to add cane sugar powder, makes granule, drying, the volatile oil and the flavorant that add above-mentioned collection are an amount of, and mixing is made the sugar-containing type granule.
Can add one or more pharmaceutically acceptable carriers in the pharmaceutical composition of the present invention, as preparation required various conventional adjuvant during different dosage form: diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant etc.
Pharmaceutical composition of the present invention can be by oral, injection or mucosa delivery, can make tablet, capsule, powder, granule, lozenge, suppository, or multiple medicament forms such as oral liquid or aseptic parenteral suspension liquid preparation, also have big or injection forms such as small-volume injection, freeze-dried powder or aseptic powder separation dose.The medicine of above-mentioned various dosage forms all can be according to the conventional method preparation of pharmaceutical field.
Pharmaceutical composition of the present invention can feed additive form join in the feedstuff of animal, improve the ability of zooprophylazis bird flu, or treatment suffers from the animal of bird flu.
Pharmaceutical composition of the present invention or additive, its effective dose are 20-80mg/kg body weight sky; Preferred dose is 30-65mg/kg body weight sky.
Pharmaceutical composition of the present invention with natural plants as crude drug, bird flu virus had the obvious suppression effect, medicine that is prepared into or additive, have advantages such as toxicity is little, effect is strong, safe and effective, open up new approach for the control of bird flu virus, have important social value, economic worth and wide application prospect.
The specific embodiment
Below further illustrate pharmaceutical composition of the present invention by experimental example and compare the beneficial effect that existing anti-avian influenza medicine has.These experimental example comprise the cytology and the zoology test of pharmaceutical composition of the present invention.
Experimental example 1
In the following experimental example.
Pharmaceutical composition of the present invention is to the protection effect of the chicken of infection bird flu virus
Test is the yellow chicken of high-quality in 50 day age with chicken, and Zhongshan University's animal experiment chicken house is bought.Pharmaceutical composition of the present invention is the granule of embodiment 5 preparation among the application, is provided by beautiful pearl group; One of control drug rimantadine is purchased the pharmaceutical Co. Ltd in Zhejiang Yu Kang, two according to Chinese patent 200510011432.3 preparation.Strain is: H5 blood serum subtype bird flu virus (1.0 * 10
-6).
Test method:
Get 190 of the yellow chickens of high-quality in 50 day age, be divided into 5 groups at random, 30 of normal control groups, all the other 40.The chick embryo allantoic liquid seat dilution that will contain bird flu virus is 0.5 * 10
-5, every chicken abdominal part injection 0.2ml inoculation.Respectively organized administration the same day at inoculation AIV, normal healthy controls group and infection matched group are fed normal saline, and feed once every day, fed 8 days continuously.The normal healthy controls group is the A group, pharmaceutical composition group of the present invention (10mg every day) is the B group, one of control drug rimantadine (10mg every day) is the C group, and two (10mg every day) that prepare control drug according to Chinese patent 200510011432.3 schemes are the D group, and infecting matched group is the E group.The results are shown in Table 1:
Table 1
Group | Quantity | Processing mode | Death toll | Mortality rate | Effective percentage |
A | 30 | Do not infect | 0 | - | - |
B | 40 | Infection, administration | 2 | 5% | 95% |
C | 40 | Infection, administration | 23 | 57.5% | 42.5% |
D | 40 | Infection, administration | 16 | 40% | 60% |
E | 40 | Infection, not administration | 37 | 92.5% | - |
As can be seen from Table 1, pharmaceutical composition of the present invention has good protection effect to the chicken that infects bird flu virus, according to Chinese patent 200510011432.3 and traditional treatment medicine rimantadine better effect is arranged.
Experimental example 2
Treatment H
7The experiment of the viral pneumonia that the type bird flu virus causes
Get the Kunming white mice that laboratory animal room of Harbin Medical University provides, injection H
7Type virus is made mouse model, and the pharmaceutical composition of the present invention that uses in the experimental group is provided by beautiful pearl group.
Test method:
Experimental group and matched group have 17 mices for every group.Contrast 1 group with the intraperitoneal injection of 15ml/kg normal saline; Contrast 2 groups with the intraperitoneal injection of the general antiviral drugs Oleum Curcumae injection of 15ml/kg; Contrast 3 groups of SHUANGSULIAN injection intraperitoneal injections with 15ml/kg general treatment pneumonia; Testing 1 group of injection Radix Isatidis, Fructus Forsythiae, the Rhizoma Anemarrhenae, Herba Pogostemonis is the injection that crude drug is made, intraperitoneal injection 15ml/kg; Testing 2 groups of injection Radix Isatidis, Fructus Forsythiae, the Rhizoma Anemarrhenae, Herba Pogostemonis, Radix Glycyrrhizaes is the injection that crude drug is made, intraperitoneal injection 15ml/kg; Testing 3 groups of injection Radix Isatidis, Fructus Forsythiae, Gypsum Fibrosum, Rhizoma Phragmitis, the Rhizoma Anemarrhenae, Herba Pogostemonis is the injection that crude drug is made, intraperitoneal injection 15ml/kg; All logotype is 10 days.Each is organized mice and all puts to death collect specimens after 11 days in medication and carry out index and detect, and the results are shown in Table 2:
Table 2
Group | Produce effects | Effectively | Invalid | Dead |
Test 1 group | 9 | 4 | 4 | 3 |
Test 2 groups | 8 | 6 | 5 | 5 |
Test 3 groups | 12 | 4 | 1 | 2 |
Contrast 1 group | 0 | 2 | 15 | 13 |
Contrast 2 groups | 3 | 5 | 9 | 8 |
Contrast 3 groups | 2 | 3 | 12 | 10 |
Annotate: produce effects is meant that the state of an illness is clearly better, and body temperature is normal, and pulmonary rale reduces; Be meant that effectively sb.'s illness took a favorable turn, body temperature is normal, and pulmonary rale slightly reduces; Invalidly be meant that the state of an illness does not have and take a turn for the better or increase the weight of.
Table 2 shows with contrast to be compared for 1,2,3 group, the pharmaceutical composition that uses in 1,2,3 groups of the experimental grouies pulmonary's circulation that has clear improvement, remove platelet aggregation, eliminate pneumonia, repair injury of lung, the effect of treatment H7 type bird flu virus wherein, is tested the pharmaceutical composition comparison used in 3 groups according to the pharmaceutical composition better efficacy of using in 1,2 group.
Experimental example 3
The anti-high pathogenic avian influenza virus cell in vitro of pharmaceutical composition of the present invention is learned experimentation
The experiment medicine is the granule of embodiments of the invention 7 preparations; Control drug is oseltamivir phosphate capsule (Tamiflu, an i.e. oseltamivir phosphate Oseltamivir phosphate) Roche company product.Used cell is mdck cell (Madin-Darby canine kidney(cell line) (MDCK)), and The University of Hong Kong, China's medical college department of microbiology provides; Used virus is H
5N
1(genotype E), The University of Hong Kong, China's medical college department of microbiology provides.
Test method:
(1) cytotoxic assay: determine that by Mosmann method routine (nineteen eighty-three) drug level (CC of toxicity pathological changes appears in 50% cell
50).
(2) antiviral experiment: quantitative viral suspension is inoculated in the celliferous culture bottle, parallel 8 bottles, adsorbs after 45 minutes, change to medicinal liquid that contains series concentration or the culture fluid that does not have medicine, cultivate 20 hours (37 degrees centigrade), reach 50% back with no medicine control bottle cytopathy and end to cultivate, and take pictures.Experimental result sees Table 3:
Table 3
Medicine | Strain | Medicinal liquid contains crude drug amount (ug/ml) | The result |
Experimental group | H
5N
1(genotype E)
| 12.5 | +8/8 |
Experimental group | H
5N
1(genotype E)
| 25 | +8/8 |
Experimental group | H
5N
1(genotype E)
| 50 | +0/8 |
Experimental group | H
5N
1(genotype E)
| 100 | +0/8 |
Positive controls | | | |
Oseltamivir phosphate capsule (Tamiflu) | H
5N
1(genotype E)
| 0.284 | +8/8 |
Oseltamivir phosphate capsule (Tamiflu) | H
5N
1(genotype E)
| 2.84 | +2/8 |
Oseltamivir phosphate capsule (Tamiflu) | H
5N
1(genotype E)
| 28.4 | +0/8 |
Annotate :+expression does not suppress
As can be seen from Table 3, when crude drug content in the injection that uses in the enforcement group reaches more than or equal to 50ug/ml, can suppress bird flu virus.
Come further to set forth the preparation method of medicine of the present invention by the following examples.
Embodiment 1: the high-capacity injection of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 1000g, Fructus Forsythiae 550g, Gypsum Fibrosum 250g, Rhizoma Phragmitis 200g, Radix Rehmanniae 300g, Herba Pogostemonis 300g, Rhizoma Acori Graminei 280g, Radix Curcumae 180g, Rhizoma Anemarrhenae 180g, be processed into pharmaceutical decocting piece, the water that adds 8 times of amounts of crude drug, soak after 3 hours, decoct and extract each 1 hour 2 times, merge extractive liquid,, filter, being evaporated to 65 ℃ of following relative densities is 1.25, cooling; Add ethanol and make and contain alcohol amount, leave standstill to 70%; Get supernatant, reclaim and eliminate ethanol, being concentrated into 65 ℃ of following relative densities is 1.15; With 2 times of amount ethyl acetate counter-current extractions, merge the ester extract, reclaim and eliminate ethyl acetate, add full dose 50% water for injection, boil, cooling, filter, add an amount of water for injection, add 0.08% tween 80, stir evenly, transfer pH to 8.0, add the sodium chloride stirring and dissolving with 40%NaOH solution, add full dose water for injection and make into isosmotic solution, use the filtering with microporous membrane of 0.22 μ m at last, embedding, sterilization, lamp inspection, packing.
Embodiment 2: the injection with small volume of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 700g, Fructus Forsythiae 350g, Gypsum Fibrosum 350g, Rhizoma Phragmitis 300g, Radix Rehmanniae 300g, Herba Pogostemonis 50g, Rhizoma Acori Graminei 30g, Radix Curcumae 30g, Rhizoma Anemarrhenae 30g, decoct with water, filter, concentrating under reduced pressure filtrate adds ethanol and leaves standstill, and filters, be evaporated to 9g medicine/ml, thin up, cold preservation, filter, concentrating under reduced pressure separates with macroporous resin, and water, NaOH solution and concentration are the ethanol drip washing of 35wt% successively, concentration is the ethanol liquid eluting of 75wt% then, collects eluent; Add the L-arginine in the eluent of dilute with water, adjusting pH to 7.5 adds active carbon, and heating and filtering is taken off charcoal, adds and the isopyknic water dilution of eluent, and it is the 4wt% of gross weight that adding L-arginine makes its concentration, promptly.
The 20ml lyophilized injectable powder of embodiment 3 preparations pharmaceutical composition of the present invention
Get Radix Isatidis 300g, Fructus Forsythiae 100g, Gypsum Fibrosum 450g, Rhizoma Phragmitis 80g, Radix Rehmanniae 150g, Herba Pogostemonis 250g, Rhizoma Acori Graminei 300g, Radix Curcumae 250g, Rhizoma Anemarrhenae 600g, adding water for injection 3200ml soaked 1 hour, add 6400ml water for injection and decoct secondary, each 1.5 hours, filter, merging filtrate obtains extracting compositions.Get and extract compositions 10g, add the injection water and make its dissolving in right amount, add sodium chloride 2.25g, adjust volume to 250ml with water for injection, add an amount of injection charcoal, boiled 20 minutes, and put coldly, filter, sterilization, irritate in low boron glass ampoule bottle by 1ml volume branch, cool drying promptly gets the lyophilized injectable powder sample.
The injection with small volume of embodiment 4 preparations pharmaceutical composition of the present invention
Get Radix Isatidis 100g, Fructus Forsythiae 50g, Gypsum Fibrosum 850g, Rhizoma Phragmitis 300g, Radix Rehmanniae 80g, Herba Pogostemonis 800g, Rhizoma Acori Graminei 80g, Radix Curcumae 80g, Rhizoma Anemarrhenae 144g, decoct with water, filter, concentrating under reduced pressure filtrate adds ethanol and leaves standstill, and filters, be evaporated to 11g medicine/ml, thin up, cold preservation, filter, concentrating under reduced pressure separates with macroporous resin, and water, NaOH solution and concentration are the ethanol drip washing of 55wt% successively, concentration is the ethanol liquid eluting of 65wt% then, collects eluent; Add the L-arginine in the eluent of dilute with water, regulate pH to 7.0, add active carbon, heating and filtering is taken off charcoal, adds and the isopyknic water dilution of eluent, promptly.
Embodiment 5: the granule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 164g, Fructus Forsythiae 650g, Gypsum Fibrosum 70g, Rhizoma Phragmitis 900g, Radix Rehmanniae 124g, Herba Pogostemonis 50g, Rhizoma Acori Graminei 90g, Radix Curcumae 100g, Rhizoma Anemarrhenae 50g, add 70wt.% ethanol in multi-function extractor, soaked overnight.The reflux, extract, secondary, each 1.5 hours, filter medicinal residues I and medicinal liquid I, medicinal liquid I places the concentrating under reduced pressure pot, reclaim under reduced pressure is to there being ethanol flavor, and is condensed into thick extractum.
With the starch oven dry, sieve, mannitol sieves, and is standby.Take by weighing the extractum of 500g and mannitol 500g, starch 150g mix homogeneously, on granulation machine, granulate with 12 order stainless steel meshs, boiled bed drying, 12 mesh sieve granulate are measured particulate content and moisture, packing, every packed 7g, sealing is preserved in shady and cool dry place
Embodiment 6: the tablet of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 110g, Fructus Forsythiae 100g, Gypsum Fibrosum 550g, Rhizoma Phragmitis 124g, Radix Rehmanniae 800g, Herba Pogostemonis 120g, Rhizoma Acori Graminei 80g, Radix Curcumae 100g, Rhizoma Anemarrhenae 300g, adding water for injection 3200ml soaked 1 hour, add 3200ml water for injection and decoct secondary, each 1 hour, filter, the reject medicinal residues, place the triple effect concentrator, stop to concentrate when being concentrated into proportion 1.08 (70 ℃), put and be chilled to room temperature, slowly add 95wt.% ethanol, make concentration of alcohol reach 50wt.%, placement is spent the night, and extracts supernatant, discards precipitate.Concentrated supernatant gets concentrated solution, adds filler 200g, mix homogeneously; Mixture is put in the granulator, added 30wt.% ethanol 60ml, granulate, drying gets final product.
2. get vitamin 50 grams, add filler 120g, mix homogeneously; Mixture is put in the granulator, added 6wt.% binding agent 35ml, granulate, drying gets final product.
3. with two groups of mix homogeneously, survey content, 33 towards the rotary tablet machine tabletting, and packing gets final product.
Embodiment 7: the tablet of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 642.9g, Fructus Forsythiae 232.1g, Gypsum Fibrosum 285.7g, Rhizoma Anemarrhenae 125g, Rhizoma Phragmitis 303.6g, Radix Rehmanniae 160.7g, Herba Pogostemonis 125g, Rhizoma Acori Graminei 125g, Radix Curcumae 125g.At first Rhizoma Anemarrhenae powder is broken into coarse powder, adds 95% alcohol heating reflux and extract 3 times, each 3 hours, filter, decompression filtrate recycling ethanol also concentrates, and obtaining relative density is the clear paste of 1.10 (50 ℃ of mensuration).8 flavors such as Radix Isatidis decoct with water three times (collecting volatile oil simultaneously), and 1 hour for the first time, the 2nd, 3 time each 0.5 hour, to filter, filtrate concentrates, and obtaining relative density is the clear paste of 1.16 (50 ℃ of mensuration).Get above-mentioned two kinds of clear paste, add lactose, sodium cyclamate is an amount of, makes 1000g lactose type granule, or add dextrin, sodium cyclamate is an amount of, makes the 1000g sugar type granules, the volatile oil and the flavorant that add above-mentioned collection again are an amount of, mixing, promptly; Or get above-mentioned two kinds of clear paste mix homogeneously, and concentrate, obtaining relative density is the clear paste of 1.30 (60 ℃), qinghuo reagent, it is an amount of to add cane sugar powder, makes granule, drying, and the volatile oil and the flavorant that add above-mentioned collection are an amount of, mixing is made sugar-containing type granule 3000g, promptly.
Embodiment 8: the capsule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 124g, Fructus Forsythiae 800g, Gypsum Fibrosum 70g, Rhizoma Phragmitis 60g, Radix Rehmanniae 300g, Herba Pogostemonis 50g, Rhizoma Acori Graminei 600g, Radix Curcumae 400g, Rhizoma Anemarrhenae 80g, add water for injection 3200ml and soaked 1 hour, add 7200ml water for injection and decoct secondary, each 1 hour, filter merging filtrate, reclaim under reduced pressure is to there not being the ethanol flavor, and being condensed into thick extractum, proportion is 1.0 (60 ℃ of surveys) relatively, places vacuum drying oven, 70 ℃ of drying under reduced pressure 36 hours, take out, pulverize, cross the 60-80 mesh sieve; With medicated powder and adjuvant mix homogeneously, sieve, granulate, oven dry, 20 mesh sieve granulate add the magnesium stearate mix homogeneously, filled capsules, promptly.
Embodiment 9: the capsule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 100g, Fructus Forsythiae 50g, Gypsum Fibrosum 70g, Rhizoma Phragmitis 864g, Rhizoma Anemarrhenae 600g, Herba Pogostemonis 800g, add water for injection 3200ml and soaked 1 hour, add 3200ml water for injection and decoct secondary, each 2.5 hours, filter merging filtrate, reclaim under reduced pressure is to there not being the ethanol flavor, and being condensed into thick extractum, proportion is 1.30 relatively, places vacuum drying oven, 80 ℃ drying under reduced pressure 48-96 hour, take out, pulverize, cross the 60-80 mesh sieve; With medicated powder and adjuvant mix homogeneously, cross 60 mesh sieves, granulate, oven dry, granulate adds the magnesium stearate mix homogeneously, filled capsules, promptly.
Embodiment 10: preparation contains the milk product (health food) of pharmaceutical composition of the present invention
Get Radix Isatidis 500g, Fructus Forsythiae 20g, Gypsum Fibrosum 600g, Rhizoma Phragmitis 20g, Radix Rehmanniae 500g, Herba Pogostemonis 344g, Rhizoma Acori Graminei 200g, Radix Curcumae 100g, Rhizoma Anemarrhenae 200g, adding water for injection 3200ml soaked 1 hour, add 3200ml water for injection and decoct secondary, each 2.5 hours, filter, merging filtrate, reclaim under reduced pressure is not distinguished the flavor of to there being ethanol, and is concentrated into proportion 1.08.
The Lac Bovis seu Bubali raw material by inspection with filtration, purification and standardization (defat is then exempted from) after, the concentrated solution that in per 100 gram emulsions (add and contain an amount of flavoring agent), adds the 0.5-6 milligram, preheating after filtration, (temperature control≤115 ℃) sterilization, homogenizing (defat is then exempted from), to cooling, after inoculating fermented bacterium (fill of coagulating type elder generation), cultivation and fermentation, to coagulate yogurt fragmentation (coagulating type is then exempted from) cooling, finished product after fill (coagulating type is then exempted from) check.
Embodiment 11: preparation contains the beverage (food) of pharmaceutical composition of the present invention
(1) get Radix Isatidis 300g, Fructus Forsythiae 550g, Gypsum Fibrosum 70g, Rhizoma Phragmitis 300g, Herba Pogostemonis 422g, Rhizoma Anemarrhenae 500g eluriate repeatedly, smash to pieces, place alkali liquor, alkali liquor is to account for the NaOH solution of drug weight 2%~3% and 0.3% sodium hexametaphosphate solution, heating is 5 minutes under 85 ℃ of temperature, pull out, flowing water dashes to float to the medicine top layer and is neutral; (2) medicine that obtains is cut into tiny lamellar, places electronic bruisher to smash and carefully be slurry, place stainless steel ware, add the edible phosphoric acid of slurry weight 2%, heating is 70 minutes in 75 ℃ of waters bath with thermostatic control, should constantly stir slurry during constant temperature; (3) add edible sodium bicarbonate the slurry neutralization be neutral, in and the time, use water cooling, do not stop to stir, slurry filters, squeezing is to doing; (4) add liquid in the filtrate and weigh 6% powdered activated carbon, insulation is 120 minutes in 88 ℃ water bath with thermostatic control, filters, and filtrate is limpid slightly faint yellow or brown, allotment, packing sterilization, by weight drug hydrolysis liquid: phosphoric acid: citric acid is 100: 3: 4 proportion liquids, will add entry in the feed liquid, and the weight ratio that makes feed liquid and water is 1: 50, mixing, bottling, gland carries out pasteurization then.
Embodiment 12: preparation contains the veterinary drug of pharmaceutical composition of the present invention
Get Radix Isatidis 600g, Fructus Forsythiae 400g, Gypsum Fibrosum 300g, Rhizoma Phragmitis 600g, Radix Rehmanniae 100g, Herba Pogostemonis 300g, Rhizoma Acori Graminei 200g, Radix Curcumae 100g, Rhizoma Anemarrhenae 100g,, obtain powder, divide packing to get final product pulverizing medicinal materials, mistake 80 mesh sieves, mixing.
Embodiment 13: the injection preventive medicine of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 1000g, Fructus Forsythiae 250g, Gypsum Fibrosum 350g, Rhizoma Phragmitis 384g, Radix Rehmanniae 70g, Herba Pogostemonis 200g, Rhizoma Acori Graminei 100g, Radix Curcumae 100g, Rhizoma Anemarrhenae 30g decocts with water, and filters concentrating under reduced pressure filtrate, add ethanol and leave standstill, filter, be evaporated to 11g medicine/ml, thin up, concentrating under reduced pressure is filtered in cold preservation, separate with macroporous resin, water, NaOH solution and concentration are the ethanol drip washing of 55wt% successively, and concentration is the ethanol liquid eluting of 65wt% then, collect eluent; Add the L-arginine in the eluent of dilute with water, regulate pH to 7.0, add active carbon, heating and filtering is taken off charcoal, adds then and the isopyknic normal saline dilution of eluent, promptly gets described injection preventive medicine.
Embodiment 14: the granule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 500g, Fructus Forsythiae 584g, Rhizoma Anemarrhenae 600g, Herba Pogostemonis 800g, add 70wt.% ethanol in multi-function extractor, soaked overnight.The reflux, extract, secondary, each 1.5 hours, filter medicinal residues I and medicinal liquid I, medicinal liquid I places the concentrating under reduced pressure pot, reclaim under reduced pressure is to there being ethanol flavor, and is condensed into thick extractum.
With the starch oven dry, sieve, mannitol sieves, and is standby.Take by weighing the extractum of 500g and mannitol 500g, starch 150g mix homogeneously, on granulation machine, granulate with 12 order stainless steel meshs, boiled bed drying, 12 mesh sieve granulate are measured particulate content and moisture, packing, every packed 7g, sealing is preserved in shady and cool dry place.
Embodiment 15: the granule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 1084g, Fructus Forsythiae 850g, Rhizoma Anemarrhenae 300g, Herba Pogostemonis 50g medical material adds 70wt.% ethanol in multi-function extractor, soaked overnight.The reflux, extract, secondary, each 1.5 hours, filter medicinal residues I and medicinal liquid I, medicinal liquid I places the concentrating under reduced pressure pot, reclaim under reduced pressure is to there being ethanol flavor, and is condensed into thick extractum.
With the starch oven dry, sieve, mannitol sieves, and is standby.Take by weighing the extractum of 500g and mannitol 500g, starch 150g mix homogeneously, on granulation machine, granulate with 12 order stainless steel meshs, boiled bed drying, 12 mesh sieve granulate are measured particulate content and moisture, packing, every packed 7g, sealing is preserved in shady and cool dry place.
Embodiment 16: the capsule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 1500g, Fructus Forsythiae 50g, Rhizoma Anemarrhenae 400g, Herba Pogostemonis 334g, Herba Andrographis 200g adds water for injection 3200ml and soaked 1 hour, add 3200ml water for injection and decoct secondary, each 2.5 hours, filter, merging filtrate, reclaim under reduced pressure is not distinguished the flavor of to there being ethanol, and is condensed into thick extractum, proportion is 1.30 relatively, place vacuum drying oven, 80 ℃ drying under reduced pressure 48-96 hour, take out, pulverize, cross the 60-80 mesh sieve; With medicated powder and adjuvant mix homogeneously, cross 60 mesh sieves, granulate, oven dry, granulate adds the magnesium stearate mix homogeneously, filled capsules, promptly.
Embodiment 17: the injection preventive medicine of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 1000g, Fructus Forsythiae 750g, Rhizoma Anemarrhenae 400g, Herba Pogostemonis 600g, Indigo Naturalis 400g, Herba Taraxaci 120g decocts with water, and filters concentrating under reduced pressure filtrate, add ethanol and leave standstill, filter, be evaporated to 11g medicine/ml, thin up, concentrating under reduced pressure is filtered in cold preservation, separate with macroporous resin, water, NaOH solution and concentration are the ethanol drip washing of 55wt% successively, and concentration is the ethanol liquid eluting of 65wt% then, collect eluent; Add the L-arginine in the eluent of dilute with water, regulate pH to 7.0, add active carbon, heating and filtering is taken off charcoal, adds then and the isopyknic normal saline dilution of eluent, promptly gets described preventive medicine.
Embodiment 18: the capsule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 500g, Fructus Forsythiae 550g, Gypsum Fibrosum 400g, Rhizoma Phragmitis 200g, Rhizoma Anemarrhenae 300g, Herba Pogostemonis 500g, Herba Andrographis 500g adds water for injection 3200ml and soaked 1 hour, add 3200ml water for injection and decoct secondary, each 2.5 hours, filter, merging filtrate, reclaim under reduced pressure is not distinguished the flavor of to there being ethanol, and is condensed into thick extractum, proportion is 1.30 relatively, place vacuum drying oven, 80 ℃ drying under reduced pressure 48-96 hour, take out, pulverize, cross the 60-80 mesh sieve; With medicated powder and adjuvant mix homogeneously, cross 60 mesh sieves, granulate, oven dry, granulate adds the magnesium stearate mix homogeneously, filled capsules, promptly.
Embodiment 19: the capsule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 300g, Fructus Forsythiae 250g, Gypsum Fibrosum 200g, Rhizoma Phragmitis 700g, Rhizoma Anemarrhenae 250g, Herba Pogostemonis 400g, Fructus Bruceae 400g adds water for injection 3200ml and soaked 1 hour, add 3200ml water for injection and decoct secondary, each 2.5 hours, filter, merging filtrate, reclaim under reduced pressure is not distinguished the flavor of to there being ethanol, and is condensed into thick extractum, proportion is 1.20 relatively, place vacuum drying oven, 80 ℃ drying under reduced pressure 48-96 hour, take out, pulverize, cross the 60-80 mesh sieve; With medicated powder and adjuvant mix homogeneously, cross 60 mesh sieves, granulate, oven dry, granulate adds the magnesium stearate mix homogeneously, filled capsules, promptly.
Embodiment 20: the syrup of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 300g, Fructus Forsythiae 250g, Gypsum Fibrosum 200g, Rhizoma Phragmitis 500g, Rhizoma Anemarrhenae 250g, Herba Pogostemonis 400g, Radix Platycodonis 380g, Radix Glycyrrhizae 400g extracts (volatile oil is standby) behind the volatile oil with steam distillation.The decocting that adds 6~8 times of medical material amounts boils 3 times, each 1h, merge 3 times medicinal liquid, filter, vacuum decompression (40 ℃) is concentrated in right amount, behind the Cryoprecipitation 24h, get supernatant and add volatile oil, simple syrup, antiseptic (sodium benzoate), distilled water to 1000ml, stir, packing, flowing steam sterilization 30min gets final product.
Embodiment 21: preparation contains the veterinary drug of pharmaceutical composition of the present invention
Get Radix Isatidis 1500g, Fructus Forsythiae 400g, Herba Pogostemonis 554g, Rhizoma Anemarrhenae 30g,, obtain powder, divide packing to get final product pulverizing medicinal materials, mistake 80 mesh sieves, mixing.
Embodiment 22: preparation contains the veterinary drug of pharmaceutical composition of the present invention
Get Radix Isatidis 100g, Fructus Forsythiae 850g, Herba Pogostemonis 800g, Rhizoma Anemarrhenae 600g,, obtain powder, divide packing to get final product pulverizing medicinal materials, mistake 80 mesh sieves, mixing.
Embodiment 23: the capsule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 100g, Fructus Forsythiae 850g, Gypsum Fibrosum 570g, Rhizoma Phragmitis 364g, Rhizoma Anemarrhenae 300g, Herba Pogostemonis 300g, add water for injection 3200ml and soaked 1 hour, add 3200ml water for injection and decoct secondary, each 2.5 hours, filter merging filtrate, reclaim under reduced pressure is to there not being the ethanol flavor, and being condensed into thick extractum, proportion is 1.30 relatively, places vacuum drying oven, 80 ℃ drying under reduced pressure 48-96 hour, take out, pulverize, cross the 60-80 mesh sieve; With medicated powder and adjuvant mix homogeneously, cross 60 mesh sieves, granulate, oven dry, granulate adds the magnesium stearate mix homogeneously, filled capsules, promptly.
Embodiment 24: the granule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 1000g, Fructus Forsythiae 700g, Rhizoma Anemarrhenae 584g, Herba Pogostemonis 200g, add 70wt.% ethanol in multi-function extractor, soaked overnight.The reflux, extract, secondary, each 1.5 hours, filter medicinal residues I and medicinal liquid I, medicinal liquid I places the concentrating under reduced pressure pot, reclaim under reduced pressure is to there being ethanol flavor, and is condensed into thick extractum.
With the starch oven dry, sieve, mannitol sieves, and is standby.Take by weighing the extractum of 500g and mannitol 500g, starch 150g mix homogeneously, on granulation machine, granulate with 12 order stainless steel meshs, boiled bed drying, 12 mesh sieve granulate are measured particulate content and moisture, packing, every packed 7g, sealing is preserved in shady and cool dry place.
Embodiment 25: the tablet of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 300g, Fructus Forsythiae 250g, Herba Pogostemonis 600g, Rhizoma Anemarrhenae 500g, add water for injection 3200ml and soaked 1 hour, add 3200ml water for injection and decoct secondary, each 1 hour, filter the reject medicinal residues, place the triple effect concentrator, stop to concentrate when being concentrated into proportion 1.08 (70 ℃), put and be chilled to room temperature, slowly add 95% ethanol of amount of calculation, make concentration of alcohol reach 50%, placement is spent the night, and extracts supernatant, discards precipitate.Concentrated supernatant gets concentrated solution, adds filler 200g, mix homogeneously; Mixture is put in the granulator, added 30wt.% ethanol 60ml, granulate, drying gets final product.
2. get vitamin 150 grams, add filler 684g, mix homogeneously; Mixture is put in the granulator, added 6wt.% binding agent 35ml, granulate, drying gets final product.
3. with two groups of mix homogeneously, survey content, 33 towards the rotary tablet machine tabletting, and packing gets final product.
Embodiment 26: the granule of preparation pharmaceutical composition of the present invention
Get Radix Isatidis 1000g, Fructus Forsythiae 400g, Rhizoma Anemarrhenae 600g, Herba Pogostemonis 200g.At first Rhizoma Anemarrhenae powder is broken into coarse powder, adds 95% alcohol heating reflux and extract 3 times, each 3 hours, filter, decompression filtrate recycling ethanol also concentrates, and obtaining relative density is the clear paste of 1.10 (50 ℃ of mensuration).8 flavors such as Radix Isatidis decoct with water three times (collecting volatile oil simultaneously), and 1 hour for the first time, the 2nd, 3 time each 0.5 hour, to filter, filtrate concentrates, and obtaining relative density is the clear paste of 1.16 (50 ℃ of mensuration).Get above-mentioned two kinds of clear paste, add lactose, sodium cyclamate is an amount of, makes 1000g lactose type granule, or add dextrin, sodium cyclamate is an amount of, makes the 1000g sugar type granules, the volatile oil and the flavorant that add above-mentioned collection again are an amount of, mixing, promptly; Or get above-mentioned two kinds of clear paste mix homogeneously, and concentrate, obtaining relative density is the clear paste of 1.30 (60 ℃), qinghuo reagent, it is an amount of to add cane sugar powder, makes granule, drying, and the volatile oil and the flavorant that add above-mentioned collection are an amount of, mixing is made sugar-containing type granule 3000g, promptly.