Technical background
Radix Glycyrrhizae had several thousand in the application of China, the content of polysaccharide is higher in the Radix Glycyrrhizae, its average content of bibliographical information is 2%~3%, and it is root, the stem of Radix Glycyrrhizae that existing CN 1343729A discloses patent application 0124539.2 " Angelica Polysaccharide " raw material that this patent adopted, through the method for decocting in water, extract clear liquid, decolouring concentrates alcohol precipitation, crude polysaccharides is dried, grinds, sieves, got to centrifugal precipitating thing; Add water by crude polysaccharides, filter swelling down at 4 ℃; Get supernatant after centrifugal again; Add Deproteinization reagent (Sevage), remove Deproteinization, dialyse with deionized water; DEAE-Cellulose (DE-32) column chromatography; Eluting concentrates, alcohol precipitation, and centrifugal, alcohol is washed, vacuum drying,
Obtain Angelica Polysaccharide.This product can activating macrophage, and the TB lymphocyte strengthens humoral immunization and cellular immunization, improves the general immunity function and more effectively suppresses the purpose of tumor and AIDS.Other has CN1387855A to disclose patent application 01118420.5 " licorice polysaccharide powder injection " raw material that this patent adopted is root, the stem of Radix Glycyrrhizae, through the method for decocting in water, extracts clear liquid, decolouring concentrates alcohol precipitation, crude polysaccharides is dried, grinds, sieves, got to centrifugal precipitating thing; Add water by crude polysaccharides, filter swelling down at 4 ℃; Get supernatant after centrifugal again; Add Deproteinization reagent (Sevage), remove Deproteinization, dialyse with deionized water; DEAE-Cellulose (DE-32) column chromatography; Eluting concentrates, alcohol precipitation, and centrifugal, alcohol is washed, and vacuum drying obtains licorice polysaccharide powder injection, and this product can activating macrophage, and the TB lymphocyte strengthens humoral immunization and cellular immunization, improves the general immunity function and more effectively suppresses the purpose of tumor and AIDS.
But still not having Angelica Polysaccharide at present is used to cure mainly chronic and recurrent respiratory tract infection new medical use and pharmaceutical preparation thereof.
Summary of the invention
The objective of the invention is to clearly propose the Angelica Polysaccharide new medical use and be feedstock production pharmaceutical preparation with the Angelica Polysaccharide.
The objective of the invention is to be achieved by the following scheme, it provides Angelica Polysaccharide new medical use and pharmaceutical preparation thereof, it is characterized in that Angelica Polysaccharide is preparing as the application for the treatment of in chronic and the recurrent respiratory tract infection medicine.
Chronic and the recurrent respiratory tract infection pharmaceutical preparation of a kind of treatment is characterized in that containing Angelica Polysaccharide and one or more pharmaceutically admissible excipient that the treatment effective dose is arranged, or can with the other medicines of Angelica Polysaccharide prescription.
Chronic and the recurrent respiratory tract infection pharmaceutical preparation of described treatment is characterized in that containing excipient or other prescription medicine of 25%~40% Angelica Polysaccharide and 60%~75%.
Chronic and the recurrent respiratory tract infection pharmaceutical preparation of described treatment is characterized in that containing excipient or other prescription medicine of 30% Angelica Polysaccharide and 70%.
Chronic and the recurrent respiratory tract infection pharmaceutical preparation of described treatment is characterized in that said medicine is tablet, capsule, granule, suspensoid, drop pill, oral liquid, aerosol, injection.
We adopt following technical scheme for this reason: pharmacodynamics: examined or check the influence of Angelica Polysaccharide multiple dosing (14 1 17 days) to animal body fluid, cell and non-specific immunity, and to the influence of animal anti-infection ability, the result is as follows:
Angelica Polysaccharide 125,250,500 and 1000mg/Kg can obviously increase the serum 1gG content of immunocompromised mice due to cyclophosphamide and the lotus tumor, Angelica Polysaccharide 500 and 1000mg/Kg obviously increase the serum 1gG content of mice with radiation injury, show that Angelica Polysaccharide has the function of obvious increase humoral immunization.
2, after the 4-dinitrofluorobenzene contact skin sensitization, contact once more about one week and can cause the delayed hypersensitivity reaction that T is cell-mediated, Angelica Polysaccharide 250mg/Kg can increase by 2, the delayed hypersensitivity reaction of the normal mouse that the 4-dinitrofluorobenzene causes, Angelica Polysaccharide 125,500mg/Kg can increase by 2, and the delayed hypersensitivity reaction of the caused by cyclophosphamide immunocompromised mice that the 4-dinitrofluorobenzene causes shows that Angelica Polysaccharide has certain facilitation to the function of T lymphatic system immunocyte.
Angelica Polysaccharide 250mg/Kg and 500mg/Kg can obviously recover the phagocytic function of caused by cyclophosphamide immunocompromised mice, can make mice carbon clean up index K and phagocytic index α significantly increases, and show that Angelica Polysaccharide can improve the non-specific immunity of mice.
After per os is irritated stomach Angelica Polysaccharide 125,250,500 and 1000mg/Kg, can obviously increase the antibacterial ability of the serum of immunocompromised mice due to cyclophosphamide and the lotus S180 tumor.Give Angelica Polysaccharide 500mg/Kg, deadly in the 72h behind the serum infection Pseudomonas aeruginosa of mice obviously reduce, can obviously reduce the mortality rate behind the mouse infection influenza virus.Angelica Polysaccharide has significant protective effect to the gold-coloured staphylococci infecting mouse.This shows that Angelica Polysaccharide can produce the certain opposing antibacterial and the ability of viral infection by improving immunity.Details sees that Tianjin Inst. of Materia Medica is to the pharmacodynamics test of Angelica Polysaccharide enteric coatel tablets (pharmacological toxicology research data 20: Angelica Polysaccharide enteric coatel tablets Pharmacodynamic test of active extract data and documents and materials and pharmacological toxicology research data 21: general pharmacodynamics test data of Angelica Polysaccharide enteric coatel tablets and documents and materials, attached).
The pharmacology: examined or check the influence of Angelica Polysaccharide to central nervous system of mice, the result shows that the filling stomach gives Angelica Polysaccharide 0.5,1,2g/Kg does not all make significant difference to mice behavior, autonomic activities, pentobarbital sodium subliminal hypnosis synergism and balance exercise.To the unify influence of respiratory system of cardiovascular system, the result shows with anesthetized dog research Angelica Polysaccharide, irritates Angelica Polysaccharide 0.1,0.2, the 2g/Kg that stomach gives the maximum volume Cmax anaesthetized dog blood pressure, heart rate and electrocardiographic wave are not had obvious influence; Heart rate has the trend of slowing down but 0.4g/Kg makes dog, but with administration before there was no significant difference relatively.Conclusion is: Angelica Polysaccharide does not have tangible adverse effect to central nervous system, the cardiovascular system of the animal respiratory system cardiovascular system respiratory system of unifying of unifying.
Acute toxicity: the application mice carries out acute toxicity test and shows that once irritate the Angelica Polysaccharide that stomach gives the maximum volume Cmax, mice does not have death and poisoning symptom, and maximum dosage-feeding is 6g/Kg.Be equivalent to 200 times of clinical plan recommended dose (1.8g/60Kg/ day).After the filling stomach gives Angelica Polysaccharide, the mice no abnormality seen, feed in 7 days, drinking-water and body weight gain speed are all normal.
Long term toxicity: rat oral gavage gives continuous 90 days of Angelica Polysaccharide 600,1200,2400g/Kg.Three dosed administration groups all produce obviously influence to mental act, diet and the body weight gain etc. of rat.Rarely seen 2400g/Kg dosage group male rat platelet and leucocytes reduction.Than lattice Canis familiaris L. oral administration Angelica Polysaccharide 200,600,1800g/Kg dosage, spirit, activity, diet, feces, body weight, anus temperature, urine biochemistry, hematology, the blood biochemical of animal be there is no obvious influence.From interim result can illustrate rat, than 90 days safe doses of lattice Canis familiaris L. administration be respectively 1200,1800g/Kg.Pharmacological toxicology test details is seen Tianjin Inst. of Materia Medica (pharmacological toxicology research data 22: Angelica Polysaccharide enteric coatel tablets acute toxicity test data and documents and materials, pharmacological toxicology research data 23: Angelica Polysaccharide chronicity toxicity test data and documents and materials, attached).
Have replenishing QI to invigorate the spleen by evidence this product, can enhancing human body immunity function, cure mainly chronic and the repeatability respiratory tract infection evident in efficacy, have no side effect, and steady quality.
Press practice of pharmacy, Angelica Polysaccharide of the present invention can be prepared into multiple pharmaceutical dosage form as curing mainly chronic and repeatability respiratory tract infection medicine, said pharmaceutical preparation is selected from a kind of in the middle of tablet, capsule, granule, suspensoid, drop pill, oral liquid, aerosol, the injection.Adjuvant in the medicine of the present invention refers to conventional excipient, and the adjuvant in the medicine of the present invention refers to: calcium hydrogen phosphate, microcrystalline Cellulose, polyvinylpolypyrrolidone, silicon dioxide, magnesium stearate, 50% ethanol, hypromellose, titanium dioxide, 70% ethanol, acrylic resin L 100-55, triethyl citrate, Pulvis Talci, titanium dioxide, color lake, 95% ethanol.
It is chronic as follows with recurrent respiratory tract infection Angelica Polysaccharide method for preparing tablet thereof to the invention provides a kind of treatment:
Angelica Polysaccharide tablet material consumption proportion: 25%~40% Angelica Polysaccharide and 60%~75% excipient or other prescription medicine,
Raw material optimised quantity proportioning: 30% Angelica Polysaccharide and 70% excipient or other prescription medicine.
The plain piece preparation method of Angelica Polysaccharide: raw material is crossed 80 mesh sieves, and it is standby that adjuvant is crossed 100 mesh sieves; Take by weighing recipe quantity adjuvant mix homogeneously earlier, with the Angelica Polysaccharide mix homogeneously, use 50% alcohol granulation again, 24 mesh sieve system soft materials, 55 ℃ of oven dry 2h, 24 mesh sieve granulate, standby; Above-mentioned granule is heavy according to the labelled amount sheet, with special-shaped stamping.
Angelica Polysaccharide enteric coated tablet preparation method: at first, prepare plain sheet according to the plain piece preparation method of above-mentioned Angelica Polysaccharide; Hypromellose, the titanium dioxide of recipe quantity are scattered in 70% ethanol, and fully mix homogeneously gets isolated layer film clothing liquid;
Plain sheet is placed coating pan, start aerator, making the sheet bed is 40 ℃, sprays into film-coat liquid with spray gun, and spray speed is 5ml/min, sprayed to film-coat liquid, and dry 20min, as sealing coat, purpose is the opaque disk wicking surface and increases hardness, so that enteric coated;
Under homogenizer, add acrylic resin L 100-55, triethyl citrate, Pulvis Talci, the titanium dioxide of recipe quantity in 95% ethanol successively, stir 45min, add color lake stirring 10min and make into uniform suspension, it is standby to cross 200 mesh sieves, gets enteric coating liquid;
With wrapping the slice, thin piece of sealing coat, place coating pan, start aerator, making the sheet bed is 30 ℃, sprays into enteric coating liquid with spray gun, and spray speed is 5ml/min, has sprayed to enteric coating liquid liquid, and dry 30min must enteric coated tablet;
Enteric coated tablet is spread out in clean porcelain dish, place 6h under the room temperature, both got enteric coated tablet.
Angelica Polysaccharide enteric coated tablet medicine of the present invention has replenishing QI to invigorate the spleen by evidence this product, can enhancing human body immunity function, cure mainly chronic and the repeatability respiratory tract infection evident in efficacy, have no side effect, and steady quality.
The specific embodiment
Embodiment 1: the plain sheet of preparation Angelica Polysaccharide
1) prescription: Angelica Polysaccharide 300g
Calcium hydrogen phosphate 285
Microcrystalline Cellulose 40g
Polyvinylpolypyrrolidone 35g
Silicon dioxide 35g
Magnesium stearate 10g
50% pure 270ml
Make 1000
2) preparation method: raw material is crossed 80 mesh sieves, and it is standby that adjuvant is crossed 100 mesh sieves; Take by weighing recipe quantity adjuvant (removing 15g polyvinylpolypyrrolidone and an amount of magnesium stearate) mix homogeneously earlier, with the Angelica Polysaccharide mix homogeneously, use 50% alcohol granulation again, 24 mesh sieve system soft materials, 55 ℃ of oven dry 2h, 24 mesh sieve granulate, standby;
Above-mentioned granule is added remaining polyvinylpolypyrrolidone and magnesium stearate, and abundant mix homogeneously; Heavy according to the labelled amount sheet, with special-shaped stamping, both got the plain sheet of Angelica Polysaccharide, the twice-daily of being grown up, a 1-2 sheet.
Embodiment 2: preparation Angelica Polysaccharide enteric coatel tablets
1) prescription:
1, sealing coat
The plain sheet 680g of Angelica Polysaccharide
Hypromellose 3.6g
Titanium dioxide 7.2g
70% ethanol 360ml
2, enteric coating layer
Acrylic resin L 100-55 43.5g
Triethyl citrate 4.4g
Pulvis Talci 11g
Titanium dioxide 8.7g
The color lake is an amount of
95% ethanol 790ml
Make 1000
2) preparation method: at first, prepare plain sheet according to the plain piece preparation method of above-mentioned Angelica Polysaccharide;
Hypromellose, the titanium dioxide of recipe quantity are scattered in 70% ethanol, and fully mix homogeneously gets isolated layer film clothing liquid;
Plain sheet is placed coating pan, start aerator, making the sheet bed is 40 ℃, sprays into film-coat liquid with spray gun, and spray speed is 5ml/min, sprayed to film-coat liquid, and dry 20min, as sealing coat, purpose is the opaque disk wicking surface and increases hardness, so that enteric coated;
Under homogenizer, add acrylic resin L 100-55, triethyl citrate, Pulvis Talci, the titanium dioxide of recipe quantity in 95% ethanol successively, stir 45min, add color lake stirring 10min and make into uniform suspension, it is standby to cross 200 mesh sieves, gets enteric coating liquid;
With wrapping the slice, thin piece of sealing coat, place coating pan, start aerator, making the sheet bed is 30 ℃, sprays into enteric coating liquid with spray gun, and spray speed is 5ml/min, has sprayed to enteric coating liquid liquid, and dry 30min must enteric coated tablet;
Enteric coated tablet is spread out in clean porcelain dish, place 6h under the room temperature, both got Angelica Polysaccharide enteric coated tablet, the twice-daily of being grown up, a 1-2 sheet.