CN100367979C - Freeze dried injection with heat-clearing, antibiosis and antiviral function and preparation method thereof - Google Patents
Freeze dried injection with heat-clearing, antibiosis and antiviral function and preparation method thereof Download PDFInfo
- Publication number
- CN100367979C CN100367979C CNB2004100867319A CN200410086731A CN100367979C CN 100367979 C CN100367979 C CN 100367979C CN B2004100867319 A CNB2004100867319 A CN B2004100867319A CN 200410086731 A CN200410086731 A CN 200410086731A CN 100367979 C CN100367979 C CN 100367979C
- Authority
- CN
- China
- Prior art keywords
- volatile oil
- flos lonicerae
- herba artemisiae
- artemisiae annuae
- ethanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The present invention discloses a freeze dried injection with heat-clearing, antibiosis and antiviral functions and a preparation method thereof, which is characterized in that a supercritical carbon dioxide extraction method is used for extracting sweet wormwood volatile oil and honeysuckle flower volatile oil from traditional Chinese medicine of sweet wormwood and honeysuckle flower, wherein sweet wormwood volatile oil and honeysuckle flower volatile oil are covered by HP-beta-cyclodextrin, and the stability and the dissolvability of the volatile oil are enhanced. Dregs of decoction after volatile oil is extracted are refluxed and extracted by ethanol. Ethanol extract products of dregs of decoction after volatile oil is extracted are obtained through high speed centrifugation, ultrafiltration, and separation and purification of upper macroporous resin. A volatile oil clathrate compound, ethanol extract products of dregs of decoction after volatile oil is extracted and effective parts of honeysuckle flower are mixed with pharmaceutic adjuvant to prepare the freeze dried injection. Pharmacological experiment results indicate that the freeze dried injection of the present invention has strong pharmacological functions.
Description
Affiliated technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of heat clearing away, antibiotic, antiviral lyophilized injectable powder and preparation method thereof, have another name called blue or green argentum powder injection.
Technical background
QINGYIN ZHUSHEYE is made up of Herba Artemisiae Annuae and Flos Lonicerae two flavor medicines, tool lung qi dispersing expelling pathogenic factors from the exterior, heat-clearing toxin-expelling functions are used for clinically that hyperpyrexia, micro evil wind due to the exogenous high fever disease is cold, antiperspirant is let out smooth, headache, cough or diseases such as upper respiratory tract infection such as red swelling and pain of throat, nasal obstruction, acute pulmonary sense inflammation.QINGYIN ZHUSHEYE is analgesic, antibiotic, the antiviral determined curative effect, is treatment upper respiratory tract infection, the preferable pure Chinese medicine of pneumonia.
The main effective ingredient of Herba Artemisiae Annuae is a volatile oil, contains compositions such as Camphora, eucalyptol, artemisia ketone in the oil.The main effective ingredient of Flos Lonicerae is chlorogenic acid and isochlorogenic acid, also contains volatile ingredient linalool, Flos Lonicerae alcohol etc.Patent (application number 98121802) " Qingying injection for clearing heat and resisting infection and preparation method thereof " discloses a kind of preparation method of QINGYIN ZHUSHEYE, this invention adopts steam distillation to extract volatile oil, it is long to extract temperature height, time, because volatile oil composition instability, long-time heating can cause oxidation Decomposition, and active constituent content is reduced.This is invented with decoction and alcohol sedimentation technique extraction, ethyl acetate extraction purification chlorogenic acid composition, studies show that aqueous extraction-alcohol precipitation technology (Liu Zhenli etc., Chinese patent medicine, ultrafiltration and precipitate with ethanol are to the influence of chlorogenic acid in the Flos Lonicerae, 1996,02) the chlorogenic acid rate of transform is low, loss of effective components is big, and the also inconvenience of operation on producing of the technology of organic solvent extraction, and environmental pollution is big, because hydrolysis and oxidation take place the chlorogenic acid composition easily, injection placement for a long time can cause chlorogenic acid content to reduce in addition.Above reason has all influenced stability, clinical practice and the curative effect of QINGYIN ZHUSHEYE.
The patent of any relevant blue or green silver-colored lyophilized injectable powder is not found in patent retrieval.
Summary of the invention
For these reasons, the present invention adopts supercritical carbon dioxide extraction method to extract volatile oil component in Herba Artemisiae Annuae, the Flos Lonicerae respectively, carry out enclose with the HP-beta-schardinger dextrin-, medicinal residues reuse alcohol reflux, centrifugal, ultrafiltration is also carried out the ethanol extract that separation and purification obtains extracting medicinal residues behind the volatile oil with macroporous resin, volatile oil clathrate compound, extracts that the ethanol extract of medicinal residues is mixed with into lyophilized injectable powder with pharmaceutic adjuvant behind the volatile oil.
The objective of the invention is to prepare the blue or green silver-colored freeze-dried powder of a kind of good stability, determined curative effect.
Another object of the present invention provides the preparation method of above-mentioned freeze-dried powder.
The present invention is achieved through the following technical solutions.
One. process recipes:
(1) crude drug is formed: Herba Artemisiae Annuae 2-4 weight portion, Flos Lonicerae 2-3 weight portion;
(2) get Herba Artemisiae Annuae, Flos Lonicerae drying, pulverized 20 mesh sieves, extract in the input extraction kettle, extraction temperature is 45 ℃, and pressure is 30MPa, and resolution temperature is 55 ℃, and pressure is 6MPa, and average discharge is 120kg/h, and extraction 1-3h gets Herba Artemisiae Annuae, Flos Lonicerae volatile oil, and is standby;
(3) medicinal residues add 8-12 and doubly measure 70% alcohol reflux secondary, and each 1h merges alcohol reflux liquid, decompression recycling ethanol also is concentrated into 1g crude drug/ml, high speed centrifugation, ultrafiltration, the macroporous adsorptive resins of having handled well on ultrafiltrate absorption, behind the water elution with 2-4 times of column volume, reuse 3-5 times of column volume 40%-60% ethanol water eluting got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract of medicinal residues behind the volatile oil;
(4) get Herba Artemisiae Annuae, Flos Lonicerae volatile oil, adopt saturated water solution method to carry out enclose with the HP-beta-schardinger dextrin-, the HP-beta-schardinger dextrin-adds the water heating for dissolving with the ratio of 30ml/g, be chilled to room temperature, according to Herba Artemisiae Annuae, Flos Lonicerae volatile oil: the ratio of HP-beta-schardinger dextrin-=1: 10-15 (v/g) adds Herba Artemisiae Annuae, Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain volatile oil clathrate compound;
(5) prescription of preparation of the present invention is:
Volatile oil clathrate compound 51-120 weight portion, the ethanol extract 38-65 weight portion of medicinal residues behind the extraction volatile oil, pharmaceutic adjuvant 154-252 weight portion;
(6) get above-mentioned clathrate, extract and pharmaceutic adjuvant and mix, add the dissolving of injection water, activated carbon adsorption is filtered, and adds the injection water to ormal weight, adds antioxidant, regulates pH value to 5.0-7.0, filtering with microporous membrane, and fill, lyophilization, promptly.
Supercritical carbon dioxide extraction is to have obtained the separation technology that develops rapidly in the world since the eighties, the feature of supercritical carbon dioxide extraction is to replace water or organic solvent to extract as spe medium and under the condition near room temperature with nontoxic, not residual carbon dioxide, its biggest advantage is a plurality of unit processes such as extract and separate (making with extra care) and removal solvent are integrated, simplify technological process greatly, improved production efficiency.In addition, it has also that rate of extraction is fast, selectivity good, extraction separation can be in the chamber (low) relaxing the bowels with purgatives of warm nature carry out, do not exist that dissolvent residual pollutes, series of advantages such as free from environmental pollution, the separation methods such as traditional separated from solvent, steam distillation that overcome exist in the course of processing some to the thermo-responsive or easy ruined disadvantage of chemical instability composition.The present invention adopts the volatile oil composition in supercritical carbon dioxide extraction method extraction Herba Artemisiae Annuae, the Flos Lonicerae, and the extraction temperature is low, efficient is high, and gained volatile oil reuse HP-β-CD carries out enclose.HP-β-CD is water miscible clathrate, and it is good to make injectable powder dissolubility in solution with the volatile oil of its enclose, good absorbing during injection, and the bioavailability height, the patient keenly feels little, is easy to by the acceptance of patient's happiness; And volatile oil is carried out enclose with HP-β-CD, and make it in the process of preparation, storage, transportation, be difficult for oxidation by air and go bad, increased the stability of volatile oil, improved curative effect.
Ultrafiltration technology is a kind of new isolation technics, can hold back the macromole impurity of removing in the extracting solution by molecular selectivity, the present invention takes alcohol reflux, centrifugal, ultrafiltration and macroporous resin separation and purification to obtain extracting the ethanol extract of medicinal residues behind the volatile oil, the ethanol extract of medicinal residues reaches 85%-90% in chlorogenic acid content behind the extraction volatile oil that the feasible the present invention of employing prepares, and has significantly improved the rate of transform of effective ingredient.Because the easy oxydrolysis of chlorogenic acid, the present invention has added antioxidant in lyophiled powder preparing technique, can significantly increase the stability of chlorogenic acid.Lyophilized powder active constituent content that the present invention makes is high and have dissolubility, stability preferably.Pharmacological evaluation shows that the silver-colored lyophilized injectable powder of green grass or young crops of the present invention has better pharmacological action.
Two. the check and analysis of preparation
1. the mensuration of Camphora in the preparation:
1.1 instrument and reagent: Tianjin, island GC-7A gas chromatograph, CR-1A monitor, flame ionization ditector;
The blue or green silver-colored lyophilized injectable powder (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides) of the present invention; QINGYIN ZHUSHEYE (pressing application number 98121802 patents " Qingying injection for clearing heat and resisting infection and preparation method thereof " preparation); Camphora reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute)
1.2 chromatographic condition: the chromatographic column 2.1m * stainless steel column of 3.2mm ID (is coated on the Chromosorb W.A.W.DMCS80-100 order carrier with 10% Polyethylene Glycol-20M; 150 ℃ of column temperatures, 170 ℃ of detector temperatures, flow velocity: nitrogen 40/min, hydrogen 60ml/min, air 300ml/min.
1.3 test method: get Camphora reference substance 50mg and put in the 100ml volumetric flask, be settled to scale with 50% ethanol dilution, shake up reference substance solution, lyophilized injectable powder of the present invention be dissolved into QINGYIN ZHUSHEYE with water for injection contain the identical solution of crude drug amount, get 5 component mixings respectively, need testing solution, get reference substance solution and need testing solution 2 μ l respectively, inject gas chromatograph calculates according to external standard method, the results are shown in Table 1.
Table 1 is respectively organized the comparison of preparation Camphora content
| Group | QINGYIN ZHUSHEYE | Lyophilized injectable powder of the present invention |
| Camphora (mg/ props up) | 0.6250 | 0.7109 |
2. the assay of chlorogenic acid in the preparation:
2.1 instrument and reagent: Waters high performance liquid chromatograph device (600 pumps, 2487 detectors), Millinium32 chromatography software; The blue or green silver-colored lyophilized injectable powder (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides) of the present invention; QINGYIN ZHUSHEYE (pressing application number 98121802 patents " Qingying injection for clearing heat and resisting infection and preparation method thereof " preparation); Chlorogenic acid reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute).
2.2 chromatographic condition: Symmetry C18 (3.9 * 150mm, 5 μ m) chromatographic column; Mobile phase: methanol: 0.2mol/L sodium dihydrogen phosphate (15: 85); Flow velocity: 1.0ml/min; Detect wavelength: 326nm.
2.3 experimental technique: get the chlorogenic acid reference substance is made 0.02mg/ml with methanol reference substance solution, lyophilized injectable powder of the present invention is dissolved into QINGYIN ZHUSHEYE with water for injection contains the identical solution of crude drug amount, in extracting sample solution 0.5ml to the 25ml volumetric flask, add the methanol dilution and be settled to scale, filter need testing solution, get reference substance solution 10 μ l and need testing solution 5 μ l respectively, inject chromatograph of liquid, calculate according to external standard method, the results are shown in Table 2.
The chlorogenic acid content that table 2 is respectively organized preparation compares
| Group | QINGYIN ZHUSHEYE | Lyophilized injectable powder of the present invention |
| Chlorogenic acid (mg/ props up) | 4.30 | 5.96 |
Conclusion: test us by above-mentioned check and analysis and can learn that the active constituent content of the blue or green silver-colored lyophilized injectable powder of the present invention obviously improves, and proves absolutely that technology of the present invention increases significantly than former technology, is of practical significance.Three. the check and analysis of the ethanol extract of medicinal residues behind the extraction volatile oil
1. experiment medicine: extract 1 (pressing the preparation of application number 98121802 patents " Qingying injection for clearing heat and resisting infection and preparation method thereof " preparation method)
Extract 2 (by preparation technology's preparation of the present invention, Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides)
2. experimental technique: take by weighing extract 50mg, put in the 25ml volumetric flask, be dissolved in water and be diluted to scale, shake up, precision is measured 1ml and is put in the 50ml volumetric flask, shakes up, be diluted to scale with 0.2mol/L hydrochloric acid, measure trap at the 326nm place, press chlorogenic acid (C according to spectrophotography
16H
28O
9) absorptance (E
1cm 1%) be 526 calculating, the results are shown in Table 3.
The chlorogenic acid content that table 3 is respectively organized extract compares
| Group | Extract 1 | Extract 2 |
| 1 | 2 | 3 | 1 | 2 | 3 | |
| Chlorogenic acid percentage composition (%) | 79.8 | 80.2 | 78.5 | 86.9 | 85.6 | 87.4 |
Conclusion: test the content (in chlorogenic acid) that we can learn that the present invention extracts the ethanol extract of medicinal residues behind the volatile oil by above-mentioned check and analysis and obviously improve, prove absolutely that the present invention is of practical significance.
Four. preparation stability is relatively
With lyophilized injectable powder 1 of the present invention (not adding antioxidant), lyophilized injectable powder of the present invention 2 (adding antioxidant), carried out long-term stable experiment with QINGYIN ZHUSHEYE (preparing) by application number 98121802 patents " Qingying injection for clearing heat and resisting infection and preparation method thereof ", measure the chlorogenic acid content in 0 month, June, December, 18 months, 24 months preparations respectively, the results are shown in Table 4.
Table 4 long-time stability chlorogenic acid content
| Group | 0 month | June | December | 18 months | 24 months |
| QINGYIN ZHUSHEYE (mg/ props up) lyophilized injectable powder 1 of the present invention (mg/ props up) lyophilized injectable powder 2 of the present invention (mg/ props up) | 4.30 5.29 5.29 | 4.25 5.28 5.28 | 4.22 5.20 5.31 | 4.09 5.11 5.30 | 3.97 4.99 5.27 |
By above experimental result as can be known, chlorogenic acid stability obviously improved after the lyophilized powder that adopts the present invention to prepare added antioxidant, 24 months basic no changes of chlorogenic acid content of long-time stability experiment, and chlorogenic acid content all has reduction slightly in lyophilized injectable powder 1 of the present invention (not adding antioxidant) and the QINGYIN ZHUSHEYE, proves absolutely that technology of the present invention is more scientific and reasonable.
Five. pharmacology embodiment
Reagent and animal: the blue or green silver-colored lyophilized injectable powder (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides) of the present invention;
QINGYIN ZHUSHEYE (pressing application number 98121802 patents " Qingying injection for clearing heat and resisting infection and preparation method thereof " preparation);
Staphylococcus aureus, escherichia coli, bacillus subtilis, penicillium, aspergillus niger, cereuisiae fermentum is provided by microorganism teaching and research room of Peking University; Mouse pneumonia virus Fm100 is available from institute of viruses, Beijing;
Mice (Kunming kind), 90, male and female half and half, body weight 20 ± 2g.
1. antibacterial action
1.1 experimental technique: the filter paper method is measured bacteriostasis: the filter paper of cut-off footpath 6mm, put into drug solution and soak 16h, 120 ℃ of following moist heat sterilizations are standby. respectively get 0.5ml and corresponding solid medium with above-mentioned for examination bacterium liquid, in superclean bench, make and contain the bacterium flat board, getting the filter paper that contains diffusion juice is attached to and contains on the bacterium flat board, every ware pastes 5, every bacterium is cooked 3 repetitions, antibacterial is put 37 ℃, mycete and yeast and puts in 27 ℃ the biochemical incubator and cultivate 48h, the inhibition zone size of filter paper behind mensuration 24h, the 48h, relatively fungistatic effect sees Table 5.
Table 5 pair inhibition effect for the examination strain
| For the examination strain | QINGYIN ZHUSHEYE | Lyophilized injectable powder of the present invention | ||
| Bacteriostatic diameter (mm) | Bacteriostatic diameter (mm) | |||
| 24h | 48h | 24h | 48h | |
| Staphylococcus aureus escherichia coli bacillus subtilis penicillium Aspergillus niger yeast | 9.0 10.2 5.0 6.5 6.0 6.5 | 9.0 10.5 5.0 5.5 4.5 6.0 | 9.7 11.5 6.5 7.5 6.8 7.5 | 9.5 11.7 6.5 7.5 6.0 7.0 |
Conclusion: show that by above-mentioned pharmacological evaluation silver-colored lyophilized injectable powder of green grass or young crops of the present invention and QINGYIN ZHUSHEYE relatively have better antibacterial action.
2. to the influence of pneumonitis virus infecting mouse mortality rate
2.1 experimental technique: get 90 of mices, be divided into 3 groups at random, 30 every group, after mice is anaesthetized with ether is slight, it is 1: 320 pneumonia of mice virus 0.04ml that every Mus collunarium gives titre, administration next day, administration group lumbar injection dosage is 3.9g crude drug/kg, matched group is with 0.2ml normal saline lumbar injection, successive administration 7d, observe 20d, record animal dead number the results are shown in Table 6.
The influence of table 6 pair mouse infection pneumonia mortality rate
| Group | Death toll | Mortality rate |
| Normal saline group QINGYIN ZHUSHEYE lyophilized injectable powder of the present invention | 27 21 17 | 90％ 70％ 56.67％ |
Conclusion: above The pharmacological results shows that lyophilized injectable powder of the present invention can significantly reduce mouse infection pneumonia mortality rate, and has than the better pharmacological action of QINGYIN ZHUSHEYE.
Six, preparation embodiment
Embodiment 1
(1) get Herba Artemisiae Annuae 2000g, Flos Lonicerae 2000g drying, pulverized 20 mesh sieves, extract in the input extraction kettle, extraction temperature is 45 ℃, pressure is 30MPa, and resolution temperature is 55 ℃, and pressure is 6MPa, and average discharge is 120kg/h, extraction 3h gets Herba Artemisiae Annuae, Flos Lonicerae volatile oil, and is standby;
(2) medicinal residues add 10 times of amount 70% alcohol reflux secondaries, and each 1h merges alcohol reflux liquid, decompression recycling ethanol also is concentrated into 1g crude drug/ml, high speed centrifugation, centrifugal liquid is adsorbed with the ultrafilter membrane ultrafiltration of molecular cut off 10000, the macroporous adsorptive resins of having handled well on the ultrafiltrate, behind the water elution with 3 times of column volumes, 4 times of column volumes of reuse, 50% ethanol water eluting is got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract 45g of medicinal residues behind the volatile oil;
(3) get Herba Artemisiae Annuae, Flos Lonicerae volatile oil, adopt saturated water solution method to carry out enclose with the HP-beta-schardinger dextrin-, the HP-beta-schardinger dextrin-adds the water heating for dissolving with the ratio of 30ml/g, be chilled to room temperature, according to Herba Artemisiae Annuae, Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 10 adds Herba Artemisiae Annuae, Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain volatile oil clathrate compound 51g;
(4) prescription of preparation of the present invention is:
Volatile oil clathrate compound 51g, the ethanol extract 45g of medicinal residues behind the extraction volatile oil, mannitol 154g;
(5) get above-mentioned clathrate, extract that the ethanol extract and the mannitol of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, add the injection water to ormal weight, add sodium thiosulfate 0.25g, regulate pH value to 5.0-7-0, filtering with microporous membrane, fill, lyophilization, promptly.
Embodiment 2
(1) get Herba Artemisiae Annuae 4000g, Flos Lonicerae 2000g drying, pulverized 20 mesh sieves, extract in the input extraction kettle, extraction temperature is 45 ℃, pressure is 30MPa, and resolution temperature is 55 ℃, and pressure is 6MPa, and average discharge is 120kg/h, extraction 2h gets Herba Artemisiae Annuae, Flos Lonicerae volatile oil, and is standby;
(2) medicinal residues add 12 times of amount 70% alcohol reflux secondaries, and each 1h merges alcohol reflux liquid, decompression recycling ethanol also is concentrated into 1g crude drug/ml, high speed centrifugation, centrifugal liquid is adsorbed with the ultrafilter membrane ultrafiltration of molecular cut off 30000, the macroporous adsorptive resins of having handled well on the ultrafiltrate, behind the water elution with 4 times of column volumes, 5 times of column volumes of reuse, 45% ethanol water eluting is got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract 43g of medicinal residues behind the volatile oil;
(3) get Herba Artemisiae Annuae, Flos Lonicerae volatile oil, adopt saturated water solution method to carry out enclose with the HP-beta-schardinger dextrin-, the HP-beta-schardinger dextrin-adds the water heating for dissolving with the ratio of 30ml/g, be chilled to room temperature, according to Herba Artemisiae Annuae, Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 15 adds Herba Artemisiae Annuae, Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain volatile oil clathrate compound 105g;
(4) prescription of preparation of the present invention is:
Volatile oil clathrate compound 105g, the ethanol extract 43g of medicinal residues behind the extraction volatile oil, lactose 252g;
(5) get above-mentioned clathrate, extract that the ethanol extract and the lactose of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, add the injection water to ormal weight, add arabo-ascorbic acid 0.40g, regulate pH value to 5.0-7.0, filtering with microporous membrane, fill, lyophilization, promptly.
Embodiment 3
(1) get Herba Artemisiae Annuae 4000g, Flos Lonicerae 3000g drying, pulverized 20 mesh sieves, extract in the input extraction kettle, extraction temperature is 45 ℃, pressure is 30MPa, and resolution temperature is 55 ℃, and pressure is 6MPa, and average discharge is 120kg/h, extraction 1h gets Herba Artemisiae Annuae, Flos Lonicerae volatile oil, and is standby;
(2) medicinal residues add 8 times of amount 70% alcohol reflux secondaries, and each 1h merges alcohol reflux liquid, decompression recycling ethanol also is concentrated into 1g crude drug/ml, high speed centrifugation, centrifugal liquid is adsorbed with the ultrafilter membrane ultrafiltration of molecular cut off 30000, the macroporous adsorptive resins of having handled well on the ultrafiltrate, behind the water elution with 2 times of column volumes, 4 times of column volumes of reuse, 40% ethanol water eluting is got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract 62g of medicinal residues behind the volatile oil.
(3) get Herba Artemisiae Annuae, Flos Lonicerae volatile oil, adopt saturated water solution method to carry out enclose with the HP-beta-schardinger dextrin-, the HP-beta-schardinger dextrin-adds the water heating for dissolving with the ratio of 30ml/g, be chilled to room temperature, according to Herba Artemisiae Annuae, Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 10 adds Herba Artemisiae Annuae, Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain volatile oil clathrate compound 120g;
(4) prescription of preparation of the present invention is:
Volatile oil clathrate compound 120g, the ethanol extract 62g of medicinal residues behind the extraction volatile oil, glucosan 218g;
(5) get above-mentioned clathrate, extract that the ethanol extract and the glucosan of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, add the injection water to ormal weight, add sodium ascorbate 0.40g, regulate pH value to 5.0-7.0, filtering with microporous membrane, fill, lyophilization, promptly.
Embodiment 4
(1) get Herba Artemisiae Annuae 300g, Flos Lonicerae 2000g drying, pulverized 20 mesh sieves, extract in the input extraction kettle, extraction temperature is 45 ℃, pressure is 30MPa, and resolution temperature is 55 ℃, and pressure is 6MPa, and average discharge is 120kg/h, extraction 2h gets Herba Artemisiae Annuae, Flos Lonicerae volatile oil, and is standby;
(2) medicinal residues add 10 times of amount 70% alcohol reflux secondaries, and each 1h merges alcohol reflux liquid, decompression recycling ethanol also is concentrated into 1g crude drug/ml, high speed centrifugation, centrifugal liquid is adsorbed with the ultrafilter membrane ultrafiltration of molecular cut off 10000, the macroporous adsorptive resins of having handled well on the ultrafiltrate, behind the water elution with 4 times of column volumes, 3 times of column volumes of reuse, 60% ethanol water eluting is got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract 38g of medicinal residues behind the volatile oil.
(3) get Herba Artemisiae Annuae, Flos Lonicerae volatile oil, adopt saturated water solution method to carry out enclose with the HP-beta-schardinger dextrin-, the HP-beta-schardinger dextrin-adds the water heating for dissolving with the ratio of 30ml/g, be chilled to room temperature, according to Herba Artemisiae Annuae, Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 12 adds Herba Artemisiae Annuae, Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain volatile oil clathrate compound 71g;
(4) prescription of preparation of the present invention is:
Volatile oil clathrate compound 71g, the ethanol extract 38g of medicinal residues behind the extraction volatile oil, mannitol 191g;
(5) get above-mentioned clathrate, extract that the ethanol extract and the mannitol of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, add the injection water to ormal weight, add sodium thiosulfate 0.30g, regulate pH value to 5.0-7.0, filtering with microporous membrane, fill, lyophilization, promptly.
Embodiment 5
(1) get Herba Artemisiae Annuae 2000g, Flos Lonicerae 3000g drying, pulverized 20 mesh sieves, extract in the input extraction kettle, extraction temperature is 45 ℃, pressure is 30MPa, and resolution temperature is 55 ℃, and pressure is 6MPa, and average discharge is 120kg/h, extraction 2h gets Herba Artemisiae Annuae, Flos Lonicerae volatile oil, and is standby;
(2) medicinal residues add 15 times of amount 70% alcohol reflux secondaries, and each 1h merges alcohol reflux liquid, decompression recycling ethanol also is concentrated into 1g crude drug/ml, high speed centrifugation, centrifugal liquid is adsorbed with the ultrafilter membrane ultrafiltration of molecular cut off 10000, the macroporous adsorptive resins of having handled well on the ultrafiltrate, behind the water elution with 2 times of column volumes, 3 times of column volumes of reuse, 50% ethanol water eluting is got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract 65g of medicinal residues behind the volatile oil.
(3) get Herba Artemisiae Annuae, Flos Lonicerae volatile oil, adopt saturated water solution method to carry out enclose with the HP-beta-schardinger dextrin-, the HP-beta-schardinger dextrin-adds the water heating for dissolving with the ratio of 30ml/g, be chilled to room temperature, according to Herba Artemisiae Annuae, Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 15 adds Herba Artemisiae Annuae, Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain volatile oil clathrate compound 78g;
(4) prescription of preparation of the present invention is:
Volatile oil clathrate compound 78g, the ethanol extract 65g of medicinal residues behind the extraction volatile oil, lactose 157g;
(5) get above-mentioned clathrate, extract that the ethanol extract and the lactose of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, add the injection water to ormal weight, add sodium ascorbate 0.30g, regulate pH value to 5.0-7.0, filtering with microporous membrane, fill, lyophilization, promptly.
Claims (7)
1. a heat clearing away, antibiotic, antiviral lyophilized injectable powder, its crude drug consists of Herba Artemisiae Annuae 2-4 weight portion, Flos Lonicerae 2-3 weight portion; It is characterized in that it is by the HP-beta-CD inclusion 51-120 weight portion of Herba Artemisiae Annuae, Flos Lonicerae volatile oil, extracts that the ethanol extract 38-65 weight portion and the pharmaceutic adjuvant 154-252 weight portion of medicinal residues is prepared from behind the volatile oil; Wherein volatile oil adopts supercritical extraction to obtain, and extracts the medicinal residues alcohol reflux behind the volatile oil, and extracting solution is through centrifugal, ultrafiltration, also obtain ethanol extract with the macroporous resin separation and purification; Ethanol extract is 85%-90% in chlorogenic acid content.
2. heat clearing away according to claim 1, antibiotic, antiviral lyophilized injectable powder, its preparation method is following steps:
(1) crude drug is formed: Herba Artemisiae Annuae 2-4 weight portion, Flos Lonicerae 2-3 weight portion;
(2) get Herba Artemisiae Annuae, Flos Lonicerae drying, pulverized 20 mesh sieves, extract in the input extraction kettle, extraction temperature is 45 ℃, and pressure is 30MPa, and resolution temperature is 55 ℃, and pressure is 6MPa, and average discharge is 120kg/h, and extraction 2h gets Herba Artemisiae Annuae, Flos Lonicerae volatile oil, and is standby;
(3) medicinal residues add 8-12 and doubly measure 70% alcohol reflux secondary, and each 1h merges alcohol reflux liquid, decompression recycling ethanol also is concentrated into 1g crude drug/ml, high speed centrifugation, ultrafiltration, the macroporous adsorptive resins of having handled well on ultrafiltrate absorption, behind the water elution with 2-4 times of column volume, reuse 3-5 times of column volume 40%-60% ethanol water eluting got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract of medicinal residues behind the volatile oil;
(4) get Herba Artemisiae Annuae, Flos Lonicerae volatile oil, adopt saturated water solution method to carry out enclose with the HP-beta-schardinger dextrin-, the HP-beta-schardinger dextrin-adds the water heating for dissolving with the ratio of 30ml/g, be chilled to room temperature, according to Herba Artemisiae Annuae, Flos Lonicerae volatile oil: HP-beta-schardinger dextrin-envelope-bulk to weight ratio is 1: the ratio of 10-15 adds Herba Artemisiae Annuae, Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain volatile oil clathrate compound;
(5) get above-mentioned clathrate, extract that the ethanol extract and the pharmaceutic adjuvant of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, add the injection water to ormal weight, add antioxidant, regulate pH value to 5.0-7.0, filtering with microporous membrane, fill, lyophilization, promptly.
3. heat clearing away according to claim 1 and 2, antibiotic, antiviral lyophilized injectable powder, pharmaceutic adjuvant are a kind of in mannitol or lactose or the glucosan.
4. heat clearing away according to claim 2, antibiotic, antiviral lyophilized injectable powder, antioxidant are a kind of in sodium thiosulfate, sodium ascorbate, the arabo-ascorbic acid.
5. heat clearing away according to claim 2, antibiotic, antiviral lyophilized injectable powder, wherein macroporous adsorbent resin is nonpolar or low pole.
6. heat clearing away according to claim 2, antibiotic, antiviral lyophilized injectable powder, wherein the concentration of alcohol of macroporous adsorbent resin eluting is 45%-50%.
7. heat clearing away according to claim 2, antibiotic, antiviral lyophilized injectable powder, wherein the ultrafilter membrane molecular cut off is 10000-30000.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100867319A CN100367979C (en) | 2004-10-29 | 2004-10-29 | Freeze dried injection with heat-clearing, antibiosis and antiviral function and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100867319A CN100367979C (en) | 2004-10-29 | 2004-10-29 | Freeze dried injection with heat-clearing, antibiosis and antiviral function and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1634417A CN1634417A (en) | 2005-07-06 |
| CN100367979C true CN100367979C (en) | 2008-02-13 |
Family
ID=34847443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100867319A Expired - Fee Related CN100367979C (en) | 2004-10-29 | 2004-10-29 | Freeze dried injection with heat-clearing, antibiosis and antiviral function and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100367979C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106993798A (en) * | 2017-05-16 | 2017-08-01 | 马鞍山市晶翔食品有限公司 | A kind of local flavor sweet chili sauce and its preparation |
| CN110887914A (en) * | 2019-11-11 | 2020-03-17 | 健民药业集团股份有限公司 | Radix astragali and cassia twig five-material decoction freeze-dried powder used as reference substance and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1251766A (en) * | 1998-10-20 | 2000-05-03 | 泸州医学院 | Qingying injection for clearing heat and resisting infection and its preparing process |
-
2004
- 2004-10-29 CN CNB2004100867319A patent/CN100367979C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1251766A (en) * | 1998-10-20 | 2000-05-03 | 泸州医学院 | Qingying injection for clearing heat and resisting infection and its preparing process |
Non-Patent Citations (2)
| Title |
|---|
| 青银注射液中绿原酸与樟脑的含量测定. 邱华容等.中成药，第26卷第8期. 2004 * |
| 青银注射液指纹图谱试验研究. 中国中药杂志，第29卷第2期. 2004 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1634417A (en) | 2005-07-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20230002351A (en) | Antibacterial and antiviral pharmaceutical composition and use thereof | |
| CN101422563B (en) | Traditional Chinese medicine composition for treating wean sphagitis and preparation method and quality control method thereof | |
| CN100457139C (en) | Method for preparing a Shuanhuanglian injection and the component detecting method | |
| CN101904948B (en) | Traditional Chinese medicine preparation of new Zhongsheng pill and preparation method thereof | |
| CN102772500B (en) | Relingqing Polygonum capitatum Buch-Ham ex D.Don raw material extract with anti-inflammatory action | |
| CN101152324A (en) | Method for producing Yujin composition and medicament containing the same | |
| CN101396384A (en) | Asiatic centella extract and preparation methode thereof | |
| CN102961469B (en) | Traditional Chinese medicine dispersible tablet for treating upper respiratory infection, and preparation method and quality detection method thereof | |
| CN103127196A (en) | Preparation method and application of total extractive of artemisia rupestris L | |
| WO2022022020A1 (en) | Traditional chinese medicine composition, preparation method and use | |
| CN101011481B (en) | Herba hedyotis diffusae extract, pharmaceutical preparation, preparing process and application thereof | |
| CN100443498C (en) | Use of anti-inflammatory medicine for scheelite total saponin and its saponin compound | |
| CN102805767B (en) | Heat stranguria removal granule raw material polygonum capitatum extract with anti-gonococcus effect | |
| CN102920964B (en) | Traditional Chinese medicine preparation for curing cough | |
| CN102772497B (en) | Alcohol extraction effective part of medicinal material of Relinqing granules and preparation method thereof | |
| CN108403858B (en) | Callicarpa nudiflora extract composition for treating hand-foot-and-mouth disease and application thereof | |
| CN1947747B (en) | Traditional Chinese medicine composition containing luteolin and capsule of sweeping forsythia and its preparation method and use | |
| CN100367979C (en) | Freeze dried injection with heat-clearing, antibiosis and antiviral function and preparation method thereof | |
| CN1962650A (en) | Process for preparing high-purity dehydrated andrographolide | |
| CN101134092A (en) | Traditional Chinese medicine compound preparations for treating respiratory disease and method for preparing the same | |
| CN104524273A (en) | Preparation method of Yinqiao preparation | |
| CN104820029A (en) | Content detection method for compound houttuynia cordata mixture | |
| CN101632747B (en) | Preparation technology of children cold relaxation grain | |
| CN101658542B (en) | Soft-lithospermum total phenolic acid and use thereof in pharmacy | |
| CN104367633A (en) | Medicine combination with antibacterial and synergically-antibacterial effects, and preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |