CN1947742A - Medicine composition contg. radix bupleuri and Radix scutellariae glucoside, prepn. method and use thereof - Google Patents
Medicine composition contg. radix bupleuri and Radix scutellariae glucoside, prepn. method and use thereof Download PDFInfo
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Abstract
An antibacterial and antiviral composite medicine for antipyresis and analgesia is proportionally prepared from bupleurum root or its extract and scutelloside. It has high synergistic effect and high stability.
Description
1, technical field
The present invention relates to the pharmaceutical composition of a kind of, antiviral antibiotic and antipyretic-antalgic by Radix Bupleuri and baicalin being used for of making, and its production and use, medical technical field belonged to.
2, background technology
Because to having caused showing great attention to and paying attention to of the world of medicine as spreading of many traditional antibiotic resistant such as penicillin, amoxicillin, the appearance of a large amount of appearance of multiple endurance strain and new virus makes intractable infection more and more at present.Meanwhile,, also do not produce drug resistance, thereby the excavation and the research of natural drug is come into one's own day by day because the compatibility of natural drugs such as traditional Chinese herbal medicine or the compositions of effective ingredient often have complementation, synergistic function.
Radix Bupleuri is the Chinese medicine and the conventional Chinese medicine of China, " Chinese pharmacopoeia regulation Umbelliferae herbaceos perennial Radix Bupleuri (Radix Bupleuri) BupleurumChinese DC. and Radix Bupeuri Scorzonerfolii. (Radix Bupleuri Scorzonerifolii) Bupleurum scorzonerifolium Willd. are the former plant of Chinese medicine certified products, its nature and flavor are bitter cool, have evacuate bring down a fever, effect that dispersing the stagnated live-QI to relieve the stagnation of QI, yang invigorating are lifted gas, be used for the treatment of alternate attack of chill and fever, fullness in the chest and hypochondriac pain, bitter taste deafness, headache and dizziness etc.Modern age, pharmacological research showed, Radix Bupleuri has multiple physiology biological activity, mainly contains antiinflammatory, and is analgesic, antiviral, and the antibacterium endotoxin, blood fat reducing protects the liver, and improves immunity, antitumor etc.The main effective ingredient of Radix Bupleuri is saikoside and volatile oil.
Radix Scutellariae is the dry root of labiate Radix Scutellariae Scutellaria baicalensis Georgi, and property hardship, cold is returned lung, gallbladder, spleen, large intestine, small intestine meridian, effect with heat clearing and damp drying, eliminating fire and detoxication, be used for hygropyrexia, fever disease in summer vomiting and nausea uncomfortable in chest, cough due to lung-heat, diseases such as hyperpyrexia excessive thirst.Baicalin is the effective active composition that extracts in the Radix Scutellariae, be β-maltonic acid-5,6-dihydroxy-4-oxygen-2-phenyl-4H-.alpha.-5:6-benzopyran-7, recorded into the 10th 239 pages of national drug standards chemical drugs provincial standard rising national standards of National Drug Administration (Chinese Pharmacopoeia Commission's volume), wherein regulation contains baicalin (C
21H
18O
11) must not be less than 90.0% (injection); Must not be less than 83.0% (for oral use).Baicalin is an antimicrobial drug, has pharmacological actions such as antibacterial anti-inflammatory, heat-clearing and toxic substances removing, chelated metal ions, calmness, blood pressure lowering, neuroprotective, is mainly used in diseases such as infection, pneumonia, hepatitis, hypertension.Domestic existing 5 families of baicalin raw material listing at present.The structural formula of baicalin is as shown below.
The baicalin structural formula
A large amount of pharmacology and clinical researches show, Radix Bupleuri and baicalin have good curative effect at aspects such as antibiotic, antiviral and antipyretic-antalgics.Have much though be used for the treatment of infection that pathogenic microorganism such as antibacterial, virus cause and/or the medicine with antipyretic effect at present, their big multiactions are single, or have only antibacterial action, or have only antivirus action, and its application is limited to.Urgent need is a kind of at present has medicine antibiotic, antivirus action simultaneously, and dosage is little, produce effects is fast, and toxic and side effects is little.Utilize the interaction of Radix Bupleuri and baicalin at present, composition of prescription is used for the medicine of aspects such as antibiotic, antiviral, does not appear in the newspapers as yet.
3, summary of the invention
The purpose of this invention is to provide a kind of pharmaceutical composition that is used for antibiotic, antiviral and antipyretic-antalgic and its production and use, it is characterized in that it is made by Radix Bupleuri and baicalin, its parts by weight are: 500～8000 parts of Radix Bupleuri, 60～1000 parts of baicalins; Be preferably: 1000～4000 parts of Radix Bupleuri, 125～500 parts of baicalins; Optimum is: 2000 parts of Radix Bupleuri, 250 parts of baicalins.
More than form to be by weight as proportioning, when producing, can or reduce according to the corresponding proportion increase, as large-scale production can be raw material with the kilogram, or be unit with the ton, small-scale production can be unit with the gram also, weight can increase or reduce, but the constant rate of weight proportion between each composition.
More than form,, can make the preparation of 100～10000 consumptions,, can be made into 100～10000,1～10 of each consumption as injection as if being unit with the gram; As tablet, can be made into 100～10000, take 1～10 at every turn.
The ratio of above weight proportion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
The consumption of drug component of the present invention is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.
Radix Bupleuri recited above is to obtain Radix Bupleuri volatile oil through extracting processing, makes pharmaceutically acceptable preparation with the baicalin hybrid process again.The extracting method of Radix Bupleuri volatile oil is steam distillation or supercritical extraction, also can be by other method preparation.
Medicine of the present invention can also be made by a certain proportion of Radix Bupleuri volatile oil and baicalin, and its weight proportion is: 1: 15～500; Optimum ratio is: 1: 30～250; Optimal proportion is: 1: 180.
The invention provides the extraction process of Radix Bupleuri volatile oil, the volatile oil yield of Radix Bupleuri steam distillation is: 0.05-0.1%, the volatile oil yield of supercritical extraction is: 0.2～0.6%.It is as follows now to enumerate part technology, but is not limited only to following technology:
Technology one: vapor distillation: getting the Radix Bupleuri medicinal powder, is 5 times of amounts of sour water of 1 (adjusting of 50% sulphuric acid) with 20%NaCl, pH value, soaks 5～10 hours, and vapor distillation extracted 6 hours, collects volatile oil, promptly.Yield: 0.04%～0.06%;
Technology two: vapor distillation: get the Radix Bupleuri medicinal powder, use the low amounts of water moistening, distill, collect 7 times of amounts of distillate just, carry out the secondary vapor distillation, collect 5 times of amounts of rectification liquid, merge rectification liquid, extract with the ether jolting, about anhydrous sodium sulfate drying 12h, volatilize ether, promptly.Yield: 0.06%～0.09%;
Technology three: vapor distillation: get the Radix Bupleuri medicinal powder, with sour water immersion 5～10h of 5 times of amounts, 20%NaCl, pH=1 (sulphuric acid accent).Distill, collect after first 7 times of amounts of distillate, carry out second distillation, collect 5 times of amounts of rectification liquid, merge rectification liquid, use extracted with diethyl ether, about anhydrous sodium sulfate drying 12h, volatilize ether, promptly.Yield: 0.05%～0.07%;
Technology four: supercritical extraction: get the Radix Bupleuri medicinal powder, drop in the extraction kettle.Extraction conditions: extracting pressure is 20MPa, 30 ℃ of temperature, and extraction-container I pressure is 12MPa, 65 ℃ of temperature, extraction-container II pressure is 6MPa, 40 ℃ of temperature, extraction time 3h claims oil heavy, calculates average oil yield.Yield: 0.2%～0.6%.
Another object of the present invention is to provide a kind of and be used to prepare that treatment is antibiotic, the medicine of aspect diseases such as antiviral, antiinflammatory and antipyretic-antalgic.
That pharmaceutical composition of the present invention has is antibiotic, antiviral, antiinflammatory, antitumor, analgesia, analgesic, protect the liver, effect such as blood fat reducing, convulsion, immunomodulating.Be mainly used in flu, upper respiratory tract infection, acute and chronic hepatitis, bronchopneumonia, viral pneumonia, diseases such as heating.
Said composition can add one or more pharmaceutically acceptable carriers, with oral, snuffing is gone into or the mode of parenteral is applied to the patient who needs this treatment.Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, soft capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.; Can also be made into eye drop.The preferred form of this compositions is injection or oral formulations.
Medicine of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.
The present invention in order to increase its dissolubility, can add solubilizing agents such as tween 80 when making injection.Can add the isoosmotic adjusting agent that is used to regulate osmotic pressure in the transfusion, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.; When making oral formulations,, can be made into Benexate Hydrochloride to increase its dissolubility because the Radix Bupleuri volatile oil dissolubility is little.
The present invention proves through pharmaceutical research and drug effect animal experiment study result, is the medicine that main component is made by Radix Bupleuri and baicalin, can reduce external bacteriostatic minimal inhibitory concentration; To significant protective effect being arranged by the mice of bacterial infection; Can obviously suppress increasing of mouse peritoneal capillary permeability, good antiinflammatory action is arranged; The pneumonia that virus infected mice is caused has the obvious suppression effect; Can also raise to the rabbit body temperature that vaccine causes the obvious suppression effect is arranged.Experimental studies results of the present invention proves that Radix Bupleuri and baicalin drug combination are synergism, and drug effect obviously strengthens.
The present composition has the following advantages:
(1) provides a kind of pharmaceutical composition that is used for antibiotic, antiviral and antipyretic-antalgic and its production and use, satisfied urgent clinical needs;
(2) each proportioning of the present composition is carried out pharmacodynamic study, drawn the optimal proportion of the present composition;
(3) interaction and the composition of prescription to Radix Bupleuri and baicalin carried out pharmaceutical research, proves two medicine Synergistics, and be evident in efficacy, obviously is better than single with Radix Bupleuri or baicalin;
The every index of stability test proof medicine composition injection of the present invention of (4) carrying out is all more stable, has guaranteed safety of clinical administration.
(5) the baicalin structure is clear and definite, directly feed intake with baicalin, preparation technology is simple, the drug loss that has caused when having avoided extracting and because the different product mass discrepancy bigger shortcoming that the crude drug mass discrepancy causes, make medicine purity higher, impurity is few, and safety is higher, and mass discrepancy is little between the different batches medicine, and drug quality is more uniform and stable;
(6) Radix Bupleuri and baicalin determined curative effect, and reduced relative dosage, be with a wide range of applications.
Below routine by experiment beneficial effect of further setting forth medicine of the present invention, these experimental examples comprise the pharmacodynamic experiment of pharmaceutical composition of the present invention, the compositions of Radix Bupleuri and baicalin is hereinafter to be referred as the yellow compositions of bavin.The preparation of Radix Bupleuri wherein is according to the preparation method preparation of the technology among the embodiment 1 two.
The yellow compositions drug combination of experimental example 1 bavin drug efficacy study
Test sample: negative control group: 0.9% sodium chloride injection, self-control; Positive controls: levofloxacin injection, self-control;
Radix Bupleuri group: injection of Radix Bupleuri, self-control;
Baicalin group: baicalin for injection liquid, self-control;
The yellow composite injection of bavin (Radix Bupleuri and baicalin various dose proportioning) group: 9 groups of (bavin+Huangs=1000mg+125mg; Bavin+Huang=1000mg+250mg; Bavin+Huang=1000mg+500mg; Bavin+Huang=2000mg+125mg; Bavin+Huang=2000mg+250mg; Bavin+Huang=2000mg+500mg; Bavin+Huang=4000mg+125mg; Bavin+Huang=4000mg+250mg; Bavin+Huang=4000mg+500mg), self-control.
For trying strain: staphylococcus aureus, escherichia coli, Diplococcus pneumoniae, hemophilus influenza.
The preparation of test liquid: get negative control group, positive controls, Radix Bupleuri group, baicalin group, the yellow composite injection of bavin (Radix Bupleuri and baicalin various dose proportioning) group (bavin+Huang=1000mg+125mg; Bavin+Huang=1000mg+250mg; Bavin+Huang=1000mg+500mg; Bavin+Huang=2000mg+125mg; Bavin+Huang=2000mg+250mg; Bavin+Huang=2000mg+500mg; Bavin+Huang=4000mg+125mg; Bavin+Huang=4000mg+250mg; Bavin+Huang=4000mg+500mg), be mixed with the test liquid that concentration is 8mg/ml respectively, serial dilution is the test liquid of 4mg/ml, 2mg/ml, 1mg/ml, 0.5mg/ml, 0.25mg/ml, 0.125mg/ml.
The preparation of bacteria suspension: with above-mentioned for the examination strain with suitable slant activation after, make with sterilized water and to contain the bacterium number and be about 10
8Individual/the ml bacteria suspension.
The mensuration of minimum inhibitory concentration (MIC): preparation bacterial liquid culture medium, accurately measure 8ml by every pipe, the packing test tube, 21 of each strain packing of antibacterial, in 121.3 ℃ of warm sterilizations 20 minutes, accurately measure 8mg/ml then, 4mg/ml, 2mg/ml, 1mg/ml, 0.5mg/ml, 0.25mg/ml, 0.125mg/ml the medicine 1ml of series concentration, inject sterilized fluid medium, each concentration repeats 3 times, a kind of bacterium of each series inoculation, every test tube accurately injects the 0.1ml bacteria suspension, and antibacterial is put 37 ℃ of cultivation 1～2d in the incubator, observes the growth phenomenon.Another series is not inoculated any strain as blank.
Minimum inhibitory concentration, antibacterial OD value representation.With the OD value of 721 type spectrophotometric determination inoculums, culture fluid OD value becomes positive correlation with the interior bacterial reproduction speed of culture fluid under the 550nm wavelength; Culture after the cultivation and blank carry out colorimetric determination on 721 spectrophotometers, identical with the two absorption, do not have the minimum inhibitory concentration of the least concentration of bacteria growing as the yellow injection of bavin in the culture medium.The results are shown in Table 1.
Experimental result: the yellow compositions of bavin is compared with the minimum inhibitory concentration of negative control group, positive controls, Radix Bupleuri group, baicalin group respectively for the minimum inhibitory concentration of examination strain to each, and the former all is significantly less than next four to each minimum inhibitory concentration for the examination strain.Yellow each dosage ratio group of compositions of bavin all has tangible bacteriostasis to the antibacterial for examination, to the MIC value of staphylococcus aureus less than 0.125mg/ml, to colibacillary be 0.125mg/ml, to Diplococcus pneumoniae less than 0.125mg/ml, to hemophilus influenza is 0.5mg/ml.Wherein the dosage ratio bacteriostasis with bavin+Huang=2000mg+250mg is the strongest.Prompting Radix Bupleuri and baicalin compatibility have synergistic function.
The yellow composite injection of table 1 bavin is to the minimum inhibitory concentration (MIC) for the examination bacterium
| Group | MIC(mg/ml) | |||
| Staphylococcus aureus | Escherichia coli | Diplococcus pneumoniae | Hemophilus influenza | |
| Negative control group | 8 | ＞8 | 4 | 8 |
| Positive controls | 0.25 | 4 | 0.25 | 1 |
| The Radix Bupleuri group | 0.5 | 1 | 2 | 4 |
| The baicalin group | 0.25 | 2 | 0.25 | 2 |
| Bavin+Huang=1000mg+125mg | 0.125 | 1 | 0.125 | 1 |
| Bavin+Huang=1000mg+250mg | 0.125 | 0.5 | 0.125 | 1 |
| Bavin+Huang=1000mg+500mg | 0.125 | 0.5 | 0.125 | 1 |
| Bavin+Huang=2000mg+125mg | ＜0.125 | 0.5 | 0.125 | 0.5 |
| Bavin+Huang=2000mg+250mg | ＜0.125 | 0.125 | ＜0.125 | 0.5 |
| Bavin+Huang=2000mg+500mg | ＜0.125 | 0.25 | ＜0.125 | 0.5 |
| Bavin+Huang=4000mg+125mg | ＜0.125 | 0.5 | ＜0.125 | 0.5 |
| Bavin+Huang=4000mg+250mg | 0.125 | 0.5 | ＜0.125 | 0.5 |
| Bavin+Huang=4000mg+500mg | 0.125 | 1 | 0.125 | 1 |
Annotate: minimum inhibitory concentration is a meansigma methods in the table.
Bacteriostatic experiment in the yellow compositions mice of the experimental example 2 bavins body
Test sample: matched group: sodium chloride injection, self-control;
Radix Bupleuri group: injection of Radix Bupleuri, self-control;
Baicalin group: baicalin for injection liquid, self-control;
The yellow composite injection of bavin (Radix Bupleuri and baicalin various dose proportioning) group: 3 groups of (bavin+Huangs=2000mg+125mg; Bavin+Huang=2000mg+250mg; Bavin+Huang=2000mg+500mg), self-control.
Animal subject: 360 of healthy mices, body weight 18～22g, the male and female dual-purpose is divided into matched group, Radix Bupleuri group, baicalin group, the yellow composite injection group of bavin (bavin+Huang=2000mg+125mg at random; Bavin+Huang=2000mg+250mg; Bavin+Huang=2000mg+500mg), totally 18 groups, 20 every group.
Bacterium liquid: with 5% gastric Mucin dilution staphylococcus aureus, escherichia coli, Diplococcus pneumoniae suspension, bacteria containing amount is 10
10Individual/ml.
Experimental technique: every mouse peritoneal injection bacterium liquid 0.5ml infects, 1,6 hour lumbar injection sodium chloride injection, injection of Radix Bupleuri, baicalin for injection liquid, the yellow composite injection (bavin+Huang=2000mg+125mg of bavin respectively behind the injection bacterium liquid; Bavin+Huang=2000mg+250mg; Bavin+Huang=2000mg+500mg), dosage is 15mg/kg.Infect the back and observe 24 hours animal survival numbers, judge the drug protection effect.The results are shown in Table 2.
Experimental result: in escherichia coli, staphylococcus aureus, each treatment group of Diplococcus pneumoniae infecting mouse, the effect of the yellow composite injection group of bavin (Radix Bupleuri and baicalin various dose proportioning) obviously is better than Radix Bupleuri group, baicalin group and matched group.Wherein the strongest with the effect of the dosage ratio of bavin+Huang=2000mg+250mg.
The yellow compositions of table 2 bavin is to the protective effect of infecting mouse
| Strain | Group | The Mus number | 24h death toll (only) | Protective rate (%) |
| Staphylococcus aureus | Matched group | 20 | 18 | 10 |
| The Radix Bupleuri group | 20 | 8 | 60 | |
| The baicalin group | 20 | 6 | 70 | |
| Bavin+Huang=2000mg+125mg | 20 | 4 | 80 | |
| Bavin+Huang=2000mg+250mg | 20 | 2 | 90 | |
| Bavin+Huang=2000mg+500mg | 20 | 4 | 80 | |
| Escherichia coli | Matched group | 20 | 19 | 5 |
| The Radix Bupleuri group | 20 | 10 | 50 | |
| The baicalin group | 20 | 8 | 60 | |
| Bavin+Huang=2000mg+125mg | 20 | 4 | 80 | |
| Bavin+Huang=2000mg+250mg | 20 | 2 | 90 | |
| Bavin+Huang=2000mg+500mg | 20 | 2 | 80 | |
| Diplococcus pneumoniae | Matched group | 20 | 20 | 0 |
| The Radix Bupleuri group | 20 | 11 | 45 | |
| The baicalin group | 20 | 6 | 70 | |
| Bavin+Huang=2000mg+125mg | 20 | 4 | 80 | |
| Bavin+Huang=2000mg+250mg | 20 | 1* | 95 | |
| Bavin+Huang=2000mg+500mg | 20 | 2 | 90 |
*: mice is in moribund condition and is condemned to death.
The yellow compositions of experimental example 3 bavins is tested mouse corrosion disease
Test sample: matched group: sodium chloride injection, self-control;
Radix Bupleuri group: injection of Radix Bupleuri, self-control;
Baicalin group: baicalin for injection liquid, self-control;
The yellow composite injection group of bavin: bavin+Huang=2000mg+250mg is divided into basic, normal, high three dosage groups, self-control.
Animal subject: 60 of Kunming mouses, male, body weight 18～22g is divided into 6 groups at random.
Experimental technique: get 60 of Kunming mouses, male, be divided into 6 groups at random, 10 every group, each organizes that mice irritates respectively that stomach is given and contrast medicine and be subjected to reagent.Experiment is divided into 6 groups, gives respectively and the yellow composite injection 50mg/kg of bavin, 100mg/kg, 150mg/kg, and baicalin 150mg/kg and Radix Bupleuri 150mg/kg, other establishes one group of negative control and gives with the volume normal saline.Behind the medicine after one hour, the blue liquid 0.2ml/20g of tail vein injection 0.5% ivens, pneumoretroperitoneum was injected 1.0% acetic acid 0.2ml/20g in 10 minutes, 10 minutes pneumoretroperitoneum injection 5ml normal saline solutions, put to death mice, gently rub abdominal part 50 times, cut off skin, draw peritoneal fluid with suction pipe, photometry density under wavelength 590nm.The results are shown in Table 3.
Experimental result: each administration group all have tangible antiinflammatory action (
*P＜0.05 He
*P＜0.01), all can obviously suppress increasing of mouse peritoneal capillary permeability.Wherein the effect of the yellow compositions of bavin be better than single with Radix Bupleuri or baicalin (
#P＜0.05).Proof Radix Bupleuri and baicalin compatibility have good antiinflammatory action, and relevant with the dosage of compositions, dosage during for 150mg/kg effect best.
The yellow compositions antiinflammatory action of table 3 bavin result
| Group | Dosage (mg/kg) | Optical density (X ± SD) | Suppression ratio (%) |
| Matched group | 0.45±0.14 | ||
| The Radix Bupleuri group | 150 | 0.36±0.12 * | 17.61 |
| The baicalin group | 150 | 0.38±0.11 ** | 16.95 |
| Bavin+Huang=2000mg+250mg (low dosage) | 50 | 0.32±0.13 **# | 29.00 |
| Bavin+Huang=2000mg+250mg (middle dosage) | 100 | 0.30±0.07 *# | 37.15 |
| Bavin+Huang=2000mg+250mg (high dose) | 150 | 0.29±0.06 *# | 39.25 |
Annotate:
*P＜0.05,
*P＜0.01 is compared with matched group;
#P＜0.05 is compared with Radix Bupleuri group or baicalin group
The analgesic experiment of the yellow compositions of experimental example 4 bavins
Test sample: matched group: sodium chloride injection, self-control:
Radix Bupleuri group: injection of Radix Bupleuri, self-control;
Baicalin group: baicalin for injection liquid, self-control;
The yellow composite injection group of bavin: bavin+Huang=2000mg+250mg is divided into basic, normal, high three dosage groups, self-control.
Animal subject: healthy white big ear rabbit, male and female dual-purpose, body weight 2.4～2.8kg.In experiment a few days ago, survey the normal rectal temperature of rabbit every day 4 times, 48 of the rabbit that selects anus temperature every day to fluctuate to be no more than 0.2 ℃ are divided into 6 groups at random.
Pyrogen: typhoid fever, paratyphoid fever, second triple vaccine, commercial.
Experimental technique: the basal body temperature of animal was surveyed in experiment morning on the same day earlier, gave tame rabbit ear vein injection pyrogenicity with typhoid fever, paratyphoid fever, the second triple vaccine of 0.5ml/kg, surveyed the anus temperature after half an hour respectively, and the corresponding medicine of intravenous injection.Surveyed the anus temperature once in per 1 hour after the administration, totally 4 times, surveyed anus temperature and basic anus using warming therapy difference with different time, be the index of body temperature variation.The results are shown in Table 4.
The yellow compositions of table 4 bavin is to refrigeration function (x ± s of vaccine pyrogenicity rabbit; N=8)
| Group | Dosage (mg/kg) | Fervescence after the pyrogenicity (℃) | Different time body temperature changing value after the administration (℃) | |||
| 1h | 2h | 3h | 4h | |||
| Matched group | 100 | 1.07±0.18 | 1.36±0.15 | 1.45±0.13 | 1.08±0.16 | 0.72±0.13 |
| The Radix Bupleuri group | 100 | 1.06±0.23 | 1.11±0.16 * | 0.91±0.14 * | 0.60±0.14 * | 0.40±0.15 * |
| The baicalin group | 100 | 1.07±0.15 | 1.15±0.16 * | 0.96±0.12 * | 0.64±0.13 * | 0.45±0.12 * |
| Bavin+Huang=2000mg+250mg (low dosage) | 50 | 1.07±0.20 | 1.05±0.12 **# | 0.85±0.16 **# | 0.58±0.14 **# | 0.32±0.13 **# |
| Bavin+Huang=2000mg+250mg (middle dosage) | 75 | 1.06±0.12 | 1.02±0.13 **# | 0.83±0.12 **# | 0.54±0.17 **# | 0.31±0.15 **# |
| Bavin+Huang=2000mg+250mg (high dose) | 100 | 1.07±0.14 | 1.00±0.16 **# | 0.81±0.14 **# | 0.51±0.12 **# | 0.30±0.12 **# |
Annotate:
*P＜0.05,
*P＜0.01 is compared with matched group;
#P＜0.05 is compared with Radix Bupleuri group or baicalin group.
Experimental result: each administration group all have tangible refrigeration function (
*P＜0.05 He
*P＜0.01).Wherein the yellow compositions of bavin has the obvious suppression effect to the rabbit body temperature rising that vaccine causes, and uses Radix Bupleuri or baicalin longer duration more separately, and medication still has after 4 hours and separates thermal effect.And relevant with the dosage of compositions, effect is best during high dose.
The yellow composition injection interior resisting virus experiment of experimental example 5 bavins
Test sample: infect matched group: influenza virus liquid (FM
1), self-control;
Radix Bupleuri group: injection of Radix Bupleuri, self-control;
Baicalin group: baicalin for injection liquid, self-control;
The yellow composite injection group of bavin: bavin+Huang=2000mg+250mg is divided into basic, normal, high three dosage groups, self-control.
Animal subject: 70 of Kunming mouses, male and female half and half, body weight 18～22g is divided into 7 groups at random.
Experimental technique: get 70 of Kunming mouses, male and female half and half, be divided into 7 groups at random, be respectively and infect matched group, normal control group, Radix Bupleuri group, baicalin group, the yellow composite injection group of bavin (bavin+Huang=2000mg+250mg) is divided into basic, normal, high three dosage groups, 10 every group.Except that normal group, mice is slightly anaesthetized with ether, with 1/5 LD
50Influenza virus liquid (FM
1) the collunarium infection.Begin intraperitoneal injection the previous day from infecting, every day 2 times, continuous 5 days, wherein infected group and normal control group gave with the volume normal saline.Dissected after taking by weighing the mice body weight on the 6th day, win full lung and weigh, calculate the lung exponential quantity one by one, and obtain lung index suppression ratio.Formula: heavy (the g)/body weight (g) * 100 of lung index=lung, lung index suppression ratio %=(virus control group lung index average-experimental group lung index average)/virus control group lung index average * 100%.Experimental result sees Table 5.(annotate: the lung index is big, and expression lung weight is big, and pneumonopathy range degree is serious.)
The yellow compositions of table 5 bavin is to the pulmonary inflammatory influence (x ± s of influenza virus infecting mouse; N=10)
| Group | Dosage (mg/kg) | The lung exponential quantity | Suppression ratio (%) |
| Infect matched group | - | 1.54±0.15 | - |
| The normal control group | - | 1.08±0.12 ** | - |
| The Radix Bupleuri group | 150 | 1.40±0.15 * | 8.9 |
| The baicalin group | 150 | 1.36±0.14 * | 12.8 |
| Bavin+Huang=2000mg+250mg (low dosage) | 50 | 1.19±0.11 **# | 23.1 |
| Bavin+Huang=2000mg+250mg (middle dosage) | 100 | 1.18±0.13 **# | 24.4 |
| Bavin+Huang=2000mg+250mg (high dose) | 150 | 1.14±0.10 **# | 26.1 |
Annotate:
*P＜0.05,
*P＜0.01, compare with the infection matched group:
#P＜0.05 is compared with Radix Bupleuri group or baicalin group.
Experimental result: infect back mouse lung exponential quantity and obviously increase.Each administration group all have tangible viral infection resisting function (
*P＜0.05,
*P＜0.01), wherein the effect of the yellow compositions of bavin be better than single with Radix Bupleuri or baicalin (
#P＜0.05).The pneumonia that proof Radix Bupleuri and baicalin compatibility cause virus infected mice has the obvious suppression effect, and the lung exponential quantity obviously reduces, and the lung tissue lesion degree obviously alleviates, and relevant with the dosage of compositions, dosage during for 150mg/kg effect best.
Experimental example 6 injected in mice administration acute toxicity testings
(1) experimental technique
Test sample: the yellow composite injection of bavin (self-control, 2ml: the Radix Bupleuri extract and the baicalin 250mg that are equivalent to raw medicinal herbs 2g).
Animal subject: mice, each 40 of every group of male and female, male body weight 25～28g, female body weight 21～24g.
Route of administration: intravenous injection, lumbar injection.
Observation item: death toll, general state, body weight, cut open inspection, half lethal dose.
(2) experimental result
Require to carry out prerun according to acute toxicity test, lumbar injection and intravenous injection two route of administration all can't be measured the median lethal dose(LD 50) of medicine, also do not see tangible toxic reaction, so carry out maximum dosage-feeding test in a day.Dosage: tail vein injection 0.15ml/10g, lumbar injection 0.15ml/10g, 2 times on the one.
Death toll: do not occur dead.
General state: no abnormality seen changes.
Body weight: in administration preceding 1 day, administration day, measured in 1,3,7,14 day after the administration; No abnormality seen changes.
Cut open inspection: the heart, liver, lung, kidney etc. organize no abnormality seen to change.
(3) conclusion
Occur death in this experiment, the yellow composite injection of bavin is 0.3ml/10g to the maximum tolerated dose of male and female mouse vein and intraperitoneal injection, is equivalent to 150 times of maximum consumption 10ml of the 50kg body weight day for human beings.Show this product low toxicity, safe.
The yellow composite injection stability experiment of experimental example 7 bavins
Test sample: the yellow composite injection of bavin (self-control, Radix Bupleuri 2000mg, baicalin 250mg)
Investigation project: character, pH value, clarity
Long-time stability experimental technique and result: this product is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 6 months, 12 months, every index has no significant change, experimental result show composite injection long-term place basicly stable.
In sum, Radix Bupleuri provided by the invention and baicalin compositions have synergistic function, obviously are better than the individually dosed drug effect of Radix Bupleuri or baicalin.The stability experiment result that the yellow composite injection of bavin (self-control, Radix Bupleuri 2000mg, baicalin 250mg) is carried out shows that every index of the injection that Radix Bupleuri provided by the invention and baicalin compositions are made is all more stable, can be used for amplifying and produce.
4, the specific embodiment
The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.Radix Bupleuri volatile oil in the experimental example 2～11 preparation method can be referring to the technology among the embodiment 1 one, two, three.
The preparation of embodiment 1 Radix Bupleuri volatile oil
Technology one: vapor distillation: getting the Radix Bupleuri medicinal powder, is 5 times of amounts of sour water of 1 (adjusting of 50% sulphuric acid) with 20%NaCl, pH value, soaks 5～10 hours, and vapor distillation extracted 6 hours, collects volatile oil, promptly.Yield: 0.04%～0.06%.
Technology two: vapor distillation: get the Radix Bupleuri medicinal powder, use the low amounts of water moistening, distill, collect 7 times of amounts of distillate just, carry out the secondary vapor distillation, collect 5 times of amounts of rectification liquid, merge rectification liquid, extract with the ether jolting, about anhydrous sodium sulfate drying 12h, volatilize ether, promptly.Yield: 0.06%～0.09%.
Technology three: vapor distillation: get the Radix Bupleuri medicinal powder, sour water with 5 times of amounts, 20%NaCl, pH=1 (sulphuric acid accent) soaks 5～10h, distill, collect after first 7 times of amounts of distillate, carry out second distillation, collect 5 times of amounts of rectification liquid, merge rectification liquid, use extracted with diethyl ether, about anhydrous sodium sulfate drying 12h, volatilize ether, promptly.Yield: 0.05%～0.07%.
Technology four: supercritical extraction: get the Radix Bupleuri medicinal powder, drop in the extraction kettle.Extraction conditions: extracting pressure is 20MPa, 30 ℃ of temperature, and extraction-container I pressure is 12MPa, 65 ℃ of temperature, extraction-container II pressure is 6MPa, 40 ℃ of temperature, extraction time 3h claims oil heavy, calculates average oil yield.Yield: 0.2%～0.6%.
The Radix Bupleuri volatile oil identification experiment
(1) get each 2ml of this product, split in first, second two test tubes, the second pipe is put in the water-bath behind the evaporate to dryness, and residue adds water 2ml makes dissolving.Two pipes respectively add 2 of the 2mol/L hydrochloric acid solutions of 0.05% dinitrophenylhydrazine, and mixing adds 4～5 of 10% potassium hydroxide solutions more respectively, and first Guan Suoxian wine redness should be than second Guan Shen.
(2) get each 2ml of this product, split in two test tubes of first, second, the second pipe is put in the water-bath behind the evaporate to dryness, and residue adds water 2ml makes dissolving.Two pipes respectively add 2 of fuchsin sulfurous acid test solutions, mixing, and after placing slightly, first Guan Suoxian rose should be than second Guan Shen.
The preparation of the yellow compositions aqueous injection of embodiment 2 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Water for injection adds to 2000ml
Prepare 1000 altogether
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Water for injection adds to 2000ml
Prepare 1000 altogether
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Water for injection adds to 2000ml
Prepare 1000 altogether
2, concrete steps:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) get the water for injection of dosing amount 40%, add the polyoxyethylene sorbitan monoleate dissolving earlier fully, add the Radix Bupleuri volatile oil of recipe quantity again, the heated and stirred dissolving fully, baicalin adds a small amount of water for injection, and adds an amount of 10% sodium hydroxide solution accent pH to 9～10, and heating makes dissolving.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure and add pH value to 5～7 of dilute hydrochloric acid regulator solution.
6) through the microporous filter membrane fine straining of 0.45 μ m.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) with the solution sealing by fusing in glass ampule.
9) 100 ℃ of flowing steam sterilizations are 30 minutes.
10) while hot sample being put into 0.01% methylene blue solution hunts leak.
11) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow compositions sodium chloride transfusion of embodiment 3 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
2, concrete steps:
1) handles the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) get the water for injection of dosing amount 40%, add the polyoxyethylene sorbitan monoleate dissolving earlier fully, add the Radix Bupleuri volatile oil of recipe quantity again, the heated and stirred dissolving fully.Baicalin adds a small amount of water for injection, and adds an amount of 10% sodium hydroxide solution accent pH to 9～10, and heating makes dissolving.Sodium chloride is complete with the water for injection dissolving of dosing amount 40%.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure and add pH value to 5～7 of dilute hydrochloric acid regulator solution.
6) through the microporous filter membrane fine straining of 0.45 μ m.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow compositions glucose infusion liquid of embodiment 4 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
2, concrete steps:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) get the water for injection of dosing amount 40%, add the polyoxyethylene sorbitan monoleate dissolving earlier fully, add the Radix Bupleuri volatile oil of recipe quantity again, the heated and stirred dissolving fully.Baicalin adds a small amount of water for injection, and adds an amount of 10% sodium hydroxide solution accent pH to 9～10, and heating makes dissolving.Glucose is complete with the water for injection dissolving of dosing amount 40%.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5), measure and add pH value to 5～7 of dilute hydrochloric acid regulator solution through sand filtration rod filtering decarbonization.
6) through the microporous filter membrane fine straining of 0.45 μ m.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow composition tablet of embodiment 5 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-6g
Starch 120.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Carboxymethylstach sodium 4.0g
Prepare 1000 altogether
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-8.4g
Starch 120.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Carboxymethylstach sodium 4.0g
Prepare 1000 altogether
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-7.2g
Starch 120.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Carboxymethylstach sodium 4.0g
Prepare 1000 altogether
2, concrete steps:
1) takes by weighing raw material and adjuvant according to recipe quantity.
2) it is standby baicalin to be pulverized 100 mesh sieves, gets Radix Bupleuri volatile oil, adds in the beta-schardinger dextrin-of the modulated one-tenth pasty state of water, grinds 1 hour, and cold drying (≤60 ℃) promptly get clathrate, pulverizing, and mistake 100 mesh sieves, standby.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with Radix Bupleuri volatile oil Benexate Hydrochloride, baicalin, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) the sheet weight sheet of determining according to chemical examination.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow composition capsule of embodiment 6 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-6g
Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1.0g
Prepare 1000 altogether
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-8.4g
Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1.0g
Prepare 1000 altogether
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-7.2g
Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1.0g
Prepare 1000 altogether
2, concrete steps:
1) takes by weighing raw material and adjuvant according to recipe quantity.
2) it is standby baicalin to be pulverized 100 mesh sieves, gets Radix Bupleuri volatile oil, adds in the beta-schardinger dextrin-of the modulated one-tenth pasty state of water, grinds 1 hour, and cold drying (≤60 ℃) promptly get clathrate, pulverizing, and mistake 100 mesh sieves, standby.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with Radix Bupleuri volatile oil Benexate Hydrochloride, baicalin, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) loading amount of determining according to chemical examination incapsulates.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow composition soft agent of embodiment 7 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Soybean oil 500.0g
Soybean phospholipid 50g
Cera Flava 50g
Prepare 1000 altogether
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Soybean oil 500.0g
Soybean phospholipid 50g
Cera Flava 50g
Prepare 1000 altogether
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Soybean oil 500.0g
Soybean phospholipid 50g
Cera Flava 50g
Prepare 1000 altogether
2, concrete steps:
Radix Bupleuri volatile oil and baicalin pulverize separately are crossed 100 mesh sieves, and with the soybean oil of recipe quantity and soybean phospholipid, Cera Flava heating and melting, mixing is put coldly, adds Radix Bupleuri volatile oil and baicalin and grinds well, and is pressed into soft capsule and gets final product.
The preparation of the yellow composition granule of embodiment 8 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-6g
Icing Sugar 1000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-8.4g
Icing Sugar 1000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Beta-schardinger dextrin-7.2g
Icing Sugar 1000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
2, concrete steps:
1) takes by weighing raw material and adjuvant according to recipe quantity.
2) it is standby sucrose to be pulverized 100 mesh sieves.It is standby that baicalin was pulverized 100 mesh sieves, gets Radix Bupleuri volatile oil, adds in the beta-schardinger dextrin-of the modulated one-tenth pasty state of water, ground 1 hour, and cold drying (≤60 ℃) promptly gets clathrate, pulverizes, and crosses 100 mesh sieves, standby.
3) the method mix homogeneously that Radix Bupleuri volatile oil Benexate Hydrochloride, baicalin and Icing Sugar are progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material,
4) cross 20 mesh sieve system granules.
5) granule is dried under 60 ℃ condition.
6) dried granule is crossed 18 mesh sieve granulate.
7) sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule.
8) packing, finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow composition dripping agent of embodiment 9 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyethylene glycol 6000 600g
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyethylene glycol 6000 600g
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyethylene glycol 6000 600g
2, concrete steps:
With polyethylene glycol 6000 heating and melting in water-bath, treat to add after whole fusions Radix Bupleuri volatile oil and baicalin, stirring and dissolving, 60 mesh sieves filter, and keep 60 ℃ to splash in the liquid paraffin that is chilled to below 10 ℃ and make ball.
The yellow composition oral liquid preparation of embodiment 10 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Beta-schardinger dextrin-6g
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Beta-schardinger dextrin-8.4g
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Beta-schardinger dextrin-7.2g
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
2, concrete steps:
1) get Radix Bupleuri volatile oil, add in the beta-schardinger dextrin-of the modulated one-tenth pasty state of water, ground 1 hour, cold drying (≤60 ℃) promptly gets clathrate, pulverizes, and crosses 100 mesh sieves, and is standby.
1) earlier that polyoxyethylene sorbitan monoleate is complete with the water dissolution of dosing amount 40%, again the Radix Bupleuri volatile oil Benexate Hydrochloride is added the heated and stirred dissolving fully.Baicalin adds that to add an amount of dissolution of sodium hydroxide after the low amounts of water heating complete.
2) sodium benzoate and stevioside is complete with the water dissolution of dosing amount 20%.
3) merge above-mentioned solution, mend and add water to full dose.
4) filtering with microporous membrane of mistake 0.8 μ m.
5) semi-finished product chemical examination.
6) fill.Finished product is examined entirely, the packing warehouse-in.
The yellow compositions eye drop preparation of embodiment 11 bavins
1, prescription:
Prescription 1
Radix Bupleuri volatile oil 1g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Sodium hydroxide is an amount of
Sodium chloride 70g
Ethyl hydroxybenzoate 3.0g
Water adds to 10000ml
Prescription 2
Radix Bupleuri volatile oil 1.4g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Sodium hydroxide is an amount of
Sodium chloride 70g
Ethyl hydroxybenzoate 3.0g
Water adds to 10000ml
Prescription 3
Radix Bupleuri volatile oil 1.2g (being equivalent to Radix Bupleuri crude drug 2000g)
Baicalin 250g
Polyoxyethylene sorbitan monoleate 50g
Sodium hydroxide is an amount of
Sodium chloride 70g
Ethyl hydroxybenzoate 3.0g
Water adds to 10000ml
2, concrete steps:
1) earlier that polyoxyethylene sorbitan monoleate is complete with the water dissolution of dosing amount 40%, again Radix Bupleuri volatile oil is added the heated and stirred dissolving fully.Baicalin adds that to add an amount of dissolution of sodium hydroxide after the low amounts of water heating complete.
2) sodium chloride and ethyl hydroxybenzoate are complete with the water dissolution of dosing amount 20%.
3) merge above-mentioned solution, mend and add water to full dose.Measure and regulate pH value.
4) filtering with microporous membrane of mistake 0.8 μ m.
5) semi-finished product chemical examination.
6) fill.Finished product is examined entirely, the packing warehouse-in.
Claims (10)
1. pharmaceutical composition is characterized in that said composition made by the sharp baicalin of Radix Bupleuri, and its parts by weight are: 500～8000 parts of Radix Bupleuri, 60～1000 parts of baicalins.
2. pharmaceutical composition according to claim 1 is characterized in that the parts by weight of Radix Bupleuri and baicalin are: 1000～4000 parts of Radix Bupleuri, 125～500 parts of baicalins.
3. pharmaceutical composition according to claim 2 is characterized in that the parts by weight of Radix Bupleuri and baicalin are: 2000 parts of Radix Bupleuri, 250 parts of baicalins.
4. according to the described arbitrary pharmaceutical composition of claim 1～3, it is characterized in that described Radix Bupleuri obtains Radix Bupleuri volatile oil through extracting processing, makes pharmaceutically acceptable preparation with the baicalin hybrid process again.
5. pharmaceutical composition according to claim 4, the extracting method that it is characterized in that Radix Bupleuri volatile oil wherein is steam distillation or supercritical extraction.
6. pharmaceutical composition according to claim 1 is characterized in that this pharmaceutical composition can also be made by Radix Bupleuri volatile oil and baicalin, and its weight ratio is: 1: 15～500.
7. pharmaceutical composition according to claim 6 is characterized in that this pharmaceutical composition can also be made by Radix Bupleuri volatile oil and baicalin, and its weight ratio is: 1: 30～250.
8. according to claim 1～3,6,7 described arbitrary pharmaceutical compositions, it is characterized in that said composition can combine with acceptable accessories to make clinically any or pharmaceutically acceptable dosage form.
9. pharmaceutical composition according to claim 8 is characterized in that clinically or pharmaceutically acceptable dosage form is an injection.
10. pharmaceutical composition according to claim 8 is characterized in that clinically or pharmaceutically acceptable dosage form is a peroral dosage form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510104218 CN1947742A (en) | 2005-10-10 | 2005-10-10 | Medicine composition contg. radix bupleuri and Radix scutellariae glucoside, prepn. method and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510104218 CN1947742A (en) | 2005-10-10 | 2005-10-10 | Medicine composition contg. radix bupleuri and Radix scutellariae glucoside, prepn. method and use thereof |
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| CN1947742A true CN1947742A (en) | 2007-04-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510104218 Pending CN1947742A (en) | 2005-10-10 | 2005-10-10 | Medicine composition contg. radix bupleuri and Radix scutellariae glucoside, prepn. method and use thereof |
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| Country | Link |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104127491A (en) * | 2014-07-29 | 2014-11-05 | 成都乾坤动物药业有限公司 | Pharmaceutical composition with fever relieving effect and preparation method and application thereof |
| CN109589343A (en) * | 2017-09-30 | 2019-04-09 | 复旦大学 | A kind of Chinese medicinal effective-part composition of antipyretic and anti-inflammatory |
-
2005
- 2005-10-10 CN CN 200510104218 patent/CN1947742A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104127491A (en) * | 2014-07-29 | 2014-11-05 | 成都乾坤动物药业有限公司 | Pharmaceutical composition with fever relieving effect and preparation method and application thereof |
| CN109589343A (en) * | 2017-09-30 | 2019-04-09 | 复旦大学 | A kind of Chinese medicinal effective-part composition of antipyretic and anti-inflammatory |
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