CN1634461A - Honey suckle and baikal skullcap root freeze dried injection and its preparing method - Google Patents
Honey suckle and baikal skullcap root freeze dried injection and its preparing method Download PDFInfo
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- CN1634461A CN1634461A CN 200410091534 CN200410091534A CN1634461A CN 1634461 A CN1634461 A CN 1634461A CN 200410091534 CN200410091534 CN 200410091534 CN 200410091534 A CN200410091534 A CN 200410091534A CN 1634461 A CN1634461 A CN 1634461A
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Abstract
The invention discloses a honey suckle and baikal skullcap root freeze dried injection and its preparing method, which consists of wherein supercritical carbon dioxide extraction method is employed to extract the volatile fluids of flower of honeysuckle from Chinese medicinal honeysuckle flower, wherein the volatile fluids of honeysuckle flower, wherein the honeysuckle flower volatile oil is coated with HP-beta-CD, the dross after volatile oil extraction is extracted through ethanol backflow, and igh speed centrifuging, hyperfiltration, macroscopic adsorption resin segregation and purification are carried out to obtain the alcohol extract of the dross, the honeysuckle flower volatile oil inclusion compound, alcohol extract of dross after volatile oil extraction, baikal skullcap root glycosides are mixed with medicinal auxiliary material, so as to obtain freeze dried injection.
Description
Affiliated technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of honey suckle and baikal skullcap root freeze dried injection and preparation method thereof.
Technical background
Upper respiratory tract infection, particularly acute upper respiratory tract infection heating occupy the outpatient service first place, are commonly encountered diseases clinically.Acute upper respiratory tract infection belongs to the clinical acute disease category, is commonly encountered diseases, frequently-occurring disease, and any age bracket all can take place, as deals with improperly or delay treatment, can produce serious consequence, even threatens patient's life.Anxious because of its onset, change fast, the course of disease is shorter, clinical treatment is more thorny, in addition along with the continuous increase of Resistant strain, antibiotic use also has been subjected to certain restriction, and antibiotic is as one wishes not to the utmost to the viral infection curative effect, and patent medicine or the injection exploitation that really can rapidly and thoroughly control heating in a few hours are less.
YINHUANG ZHUSHEYE (WS3-B-3691-98) be made up of Flos Lonicerae and Radix Scutellariae two flavor medicines, Flos Lonicerae sweet cold be monarch drug, heat clearing away expelling pathogenic factors from the exterior by 19 in Chinese medicine promulgated by the ministries or commissions of the Central Government; The Radix Scutellariae bitter cold is a ministerial drug, clearing away heat-fire, two medicines share have heat clearing away, the function of detoxifcation, sore-throat relieving; Be used for acute tonsillitis, disease such as the heating due to upper respiratory tract infection and the wind-heat invading the lung, cough, pharyngalgia has curative effect preferably clinically.The main component of YINHUANG ZHUSHEYE is Flos Lonicerae extract and baicalin, and main effect is heat-clearing and toxic substances removing, antiinflammatory.YINHUANG ZHUSHEYE exists with aqueous solution state, put for a long time and be prone to precipitation, influence the quality of preparation, particularly the active ingredient chlorogenic acid in the Flos Lonicerae is unstable in solution, easily oxidative degradation, influence the curative effect of preparation, simultaneously because Flos Lonicerae extract purity is low, contain protein, compositions such as tannin, thereby injection the time is easy to generate pain, the silver yellow ejection preparation detects down by pharmacopeia injection item, the underproof phenomenon of tannin and pyrogen test is often arranged, anaphylaxis has report also the time clinically, and in addition because hydrolysis and oxidation take place the chlorogenic acid composition easily, injection placement for a long time can cause chlorogenic acid content to reduce.Above reason has all influenced stability, clinical practice and the curative effect of YINHUANG ZHUSHEYE.。
Patent CN1424084A and patent CN1398626A disclose the preparation method of silver yellow injectable powder respectively, but the two preparation method all has limitation, patent CN1398626A just changes the silver yellow liquid drugs injection of intramuscular injection into power for intravenous injection, and its preparation technology just directly feeds intake Flos Lonicerae extract and Radix Scutellariae extract; Patent CN1424084A has just set forth the advantage on the lyophilized injectable powder dosage form, also directly feeds intake with Flos Lonicerae extract and Radix Scutellariae extract and makes honey suckle and baikal skullcap root freeze dried injection.Although above-mentioned injectable powder has overcome the shortcoming of injection water injection on dosage form, but not from preparation process particularly the purification remove impurity improve the quality and the clinical efficacy of preparation itself, the while, above silver yellow preparation did not all keep the another kind of important activity composition volatile oil component in the Flos Lonicerae.
Summary of the invention
For these reasons, the present invention has improved the extraction and purification process of Flos Lonicerae, with the volatile oil component in the supercritical carbon dioxide extraction method extraction Flos Lonicerae, carry out enclose with the HP-beta-schardinger dextrin-, medicinal residues reuse alcohol reflux, high speed centrifugation, ultrafiltration also carry out the ethanol extract that separation and purification obtains extracting medicinal residues behind the volatile oil with macroporous resin, the extracting honeysuckle volatile oil clathrate compound, extract that ethanol extract, the baicalin 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 a kind of silver yellow freeze-dried powder that is rich in effective ingredient, good stability.
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) extracting honeysuckle drying was pulverized 20 mesh sieves, dropped in the extraction kettle to extract, and 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 Flos Lonicerae volatile oil, and is standby;
(2) 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, it is 3000 hollow fiber column ultrafilter that high speed centrifugation, centrifugal liquid are crossed molecular cut off, 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 35%-45% ethanol water eluting got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract of medicinal residues behind the volatile oil;
(3) extracting honeysuckle 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 Flos Lonicerae volatile oil: HP-beta-schardinger dextrin-=1: 15-20 ratio (v/g) adds Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain the Flos Lonicerae volatile oil clathrate;
(4) prescription of preparation of the present invention is:
Flos Lonicerae volatile oil clathrate 3-5 weight portion, the ethanol extract 1.2-2 weight portion of medicinal residues behind the extraction volatile oil, baicalin 4 weight portions, pharmaceutic adjuvant 10-20 weight portion;
(5) get above-mentioned clathrate, extract that ethanol extract, baicalin 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 6.5-7.5, filtering with microporous membrane, 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 the supercritical carbon dioxide extraction method extraction 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.
Hyperfiltration technique is meant under the room temperature with certain pressure and flow, utilize asymmetric microcellular structure and semipermeable membrane separating medium, filter in the cross-flow mode, solvent and small-molecule substance are passed through, polymer substance and micropartical such as protein, water soluble polymer, antibacterials etc. are by the filter membrane detention, thereby reach separation, purification, spissated new membrane isolation technics with fastest developing speed, ultrafilter membrane is held back the tannin of removing in the medicinal liquid by molecular selectivity, impurity such as protein and macromolecular saccharide, simultaneously can effectively remove antibacterial and thermal source, improve the clarity of injection, improve the quality of the pharmaceutical preparations.The present invention takes alcohol reflux, high speed centrifugation, ultrafiltration and macroporous resin separation and purification to obtain the ethanol extract that Flos Lonicerae is extracted 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 purity and 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.The present invention also measures the chlorogenic acid content of preparation with high performance liquid chromatography, and assay method more science is accurate.Lyophilized powder active constituent content that the present invention makes is high and have dissolubility, stability preferably.Pharmacological evaluation shows that honey suckle and baikal skullcap root freeze dried injection of the present invention has better pharmacological action.
Two. the check and analysis of preparation
1. the assay of chlorogenic acid in the preparation:
1.1 instrument and reagent: Waters high performance liquid chromatograph device (600 pumps, 2487 detectors), Millinium32 chromatography software; Honey suckle and baikal skullcap root freeze dried injection of the present invention (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides); YINHUANG ZHUSHEYE (Shanghai herbal pharmaceutical one factory); Chlorogenic acid reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute).
1.2 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.
1.3 experimental technique: get the chlorogenic acid reference substance is made 0.04mg/ml with methanol reference substance solution, lyophilized injectable powder of the present invention is dissolved into YINHUANG ZHUSHEYE with water for injection contains the identical solution of Flos Lonicerae extract 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 and need testing solution 5 μ l respectively, inject chromatograph of liquid, calculate according to external standard method, the results are shown in Table 1.
The chlorogenic acid content that table 1 is respectively organized preparation compares
Group YINHUANG ZHUSHEYE lyophilized injectable powder of the present invention
Chlorogenic acid (mg/ props up) 4.87 6.62
Conclusion: test us by above-mentioned check and analysis and can learn that the active constituent content of honey suckle and baikal skullcap root freeze dried injection of the present invention obviously improves, prove absolutely that technology of the present invention increases significantly than former technology, is of practical significance.
Three. the check and analysis of extract
1. experiment medicine: extract 1 (by the preparation method preparation of Flos Lonicerae extract in the YINHUANG ZHUSHEYE, Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides)
Extract 2 (ethanol extract of medicinal residues behind the Flos Lonicerae extraction volatile oil by preparation technology's preparation of the present invention, is provided by Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory)
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 2.
The chlorogenic acid content that table 2 is respectively organized extract compares
Extract 1 extract 2
Group
1 2 3 1 2 3
Chlorogenic acid percentage composition (%) 41.8 42.3 43.5 87.9 86.6 87.5
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 relatively be significantly improved, prove absolutely that the present invention is of practical significance with former Flos Lonicerae extract.
Four. preparation stability is relatively
Lyophilized injectable powder 1 of the present invention (not adding antioxidant), lyophilized injectable powder of the present invention 2 (adding antioxidant), silver yellow injectable powder 1 (by the preparation of patent CN1424084A method), silver yellow injectable powder 2 (by the preparation of patent CN1398626A method), YINHUANG ZHUSHEYE (Shanghai herbal pharmaceutical one factory) have at room temperature been carried out long-term stable experiment, measure the chlorogenic acid content in 0 month, June, December, 18 months, 24 months preparations respectively, the results are shown in Table 3.
Table 3 long-time stability chlorogenic acid content
0 month 12 months 18 months 24 months June of group
YINHUANG ZHUSHEYE (mg/ props up) 4.87 4.85 4.73 4.46 4.25
Silver yellow injectable powder 1 (mg/ props up) 4.79 4.79 4.63 4.52 4.37
Silver yellow injectable powder 2 (mg/ props up) 4.85 4.81 4.70 4.50 4.33
Lyophilized injectable powder 1 of the present invention (mg/ props up) 6.62 6.60 6.48 6.30 6.24
Lyophilized injectable powder 2 of the present invention (mg/ props up) 6.62 6.63 6.62 6.60 6.61
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 the reduction phenomenon in lyophilized injectable powder 1 of the present invention (not adding antioxidant), silver yellow injectable powder 1, silver yellow injectable powder 2 and the YINHUANG ZHUSHEYE, proves absolutely that technology of the present invention is more scientific and reasonable.
Five. pharmacology embodiment
1. refrigeration function
1.1 reagent and animal: honey suckle and baikal skullcap root freeze dried injection of the present invention (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides); YINHUANG ZHUSHEYE (Shanghai herbal pharmaceutical one factory); Typhoid fever, the B-mode triple vaccine of paratyphoid fever, Wuhan Biological Products Inst. provides, lot number 030424; The cAMP detection kit is provided by Shanghai Univ. of Traditional Chinese Medicine's Isotope Lab; TERUMO type electronic clinical thermometer; The animal rabbit, male and female dual-purpose, 2.0～2.5kg, quality certification 19-025.Provide by Tongji Medical Univ's Experimental Animal Center.
1.2 experimental technique: get body weight 2kg left and right sides healthy rabbits, after adapting to laboratory environment, survey 3 times/d of anus temperature, continuous 3d, select body temperature to be no more than 0.2 ℃ 32 of animals 38.5～39.3 ℃ and body temperature fluctuation every day, be divided into 4 groups at random: silver yellow lyophilized powder group of the present invention, model control group, normal control group, 8 every group, male and female half and half.Water 12h is can't help in fasting, after measuring the rabbit basal body temperature, except that normal group, all the other each treated animals all by 1ml/kg dosage through rabbit ear edge intravenous injection typhoid fever, the B-mode triple vaccine of paratyphoid fever, behind the vaccinate 30min, administered intramuscular, dosage is 4.8g crude drug/kg, and normal group and model group wait the dosage normal saline, and every 30min measures administration front and back rabbit body temperature, each survey body temperature is double, gets its equal value record.Behind the administration 90min, make rabbit prostrate on the rabbit platform, fixing limbs, connect syringe needle No. 5 with the 1ml syringe down in waking state, penetrate the rabbit cerebellomedullary cistern between occipital bone and the atlas, extract the about 0.8ml of cerebrospinal fluid, press 1% of cerebrospinal fluid immediately and add the EDTA anticoagulant, mixing is put cAMP content in the inspection-free survey cerebrospinal fluid.The results are shown in Table 4, table 5.
Table 4 pair triple vaccine causes the influence (x ± s) of fever in rabbit body temperature
Body temperature value added after the medication after the group basal body temperature pyrogenicity
30min body temperature 30min 60min 90min
Model group 38.89 ± 0.25 39.34 ± 0.24 1.30 ± 0.22 1.47 ± 0.26 1.25 ± 0.40
YINHUANG ZHUSHEYE group 38.90 ± 0.26 39.34 ± 0.24 0.82 ± 0.23
*0.96 ± 0.16
*0.83 ± 0.33
*
Lyophilized powder group 38.86 of the present invention ± 0.25 39.32 ± 0.25 0.40 ± 0.16
*0.74 ± 0.24
*0.40 ± 0.35
*
*P＜0.05,
*Compare with model group P＜0.01.
Table 5 pair triple vaccine causes the influence (x ± s) of fever in rabbit cerebrospinal fluid cAMP content
Group sample number cAMP content C/pmolml-1
Normal control group 8 20.79 ± 2.06
Model group 8 37.70 ± 5.20 △
YINHUANG ZHUSHEYE group 8 28.80 ± 2.86
*
Lyophilized powder group 8 23.25 ± 3.15 of the present invention
*
△Compare with normal group △ △ P＜0.01;
*P＜0.05,
*Compare with model group P＜0.01.
Result of the test shows that silver yellow freeze-dried powder of the present invention can obviously suppress the rabbit body temperature rising that triple vaccine causes, has significant refrigeration function, and has better effect than YINHUANG ZHUSHEYE; Honey suckle and baikal skullcap root freeze dried injection of the present invention and YINHUANG ZHUSHEYE group rabbit cerebrospinal fluid group cAMP content all are lower than model group, show the generation of silver yellow preparation energy inhibition maincenter heating medium cAMP, and lyophilized injectable powder effect wherein of the present invention is more obvious.
2. antibacterial action
2.1 reagent and animal: honey suckle and baikal skullcap root freeze dried injection of the present invention (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides); YINHUANG ZHUSHEYE (Shanghai herbal pharmaceutical one factory); Staphylococcus aureus, B family streptococcus are provided by Wuhan Biological Products Inst.; Kunming mouse, male, body weight 16～18g is provided by Tongji Medical Univ's Experimental Animal Center.
2.2 experimental technique: the healthy male mice of body weight 16-18g is divided into 3 groups at random, 20 every group: be respectively blank group, YINHUANG ZHUSHEYE group, lyophilized powder group of the present invention.Begin intraperitoneal injection half an hour after infecting, and successive administration 3 days, dosage are 12g crude drug/kg, and blank group waits the dosage normal saline.Depletion Staphylococcus aureus culture is inoculated among the 2mlTSB, cultivated 7 hours for 37 ℃, get among 7 hours culture 0.1ml transferred species 10mlTSB, continue to cultivate 17 hours, above-mentioned 7-17 hour culture done 7 times of dilutions with the gastric Mucin suspension, with this bacterium liquid with every Mus 0.5ml abdominal cavity infection.Get B family streptococcus culture and be inoculated in the TSB culture medium that contains 10% serum, cultivated 18 hours for 37 ℃, with this bacterium liquid with every Mus 0.5ml abdominal cavity infection.Infect the back and observe animal dead situation and calculating, the results are shown in Table 6, table 7.
The protective effect of table 6 pair infection of staphylococcus aureus dead mouse
Group number of animals (only) death toll (only) per cent death loss (%)
Matched group 20 20 100
YINHUANG ZHUSHEYE group 20 9 45
Lyophilized injectable powder 20 6 30 of the present invention
The protective effect of table 7 pair B family streptococcal infection dead mouse
Group number of animals (only) death toll (only) per cent death loss (%
Matched group 20 16 80
YINHUANG ZHUSHEYE group 20 5 25
Lyophilized injectable powder 20 2 10 of the present invention
Result of the test shows that lyophilized powder of the present invention can obviously reduce infection of staphylococcus aureus mice and B family streptococcal infection mortality of mice, and has than the better effect of YINHUANG ZHUSHEYE.
Six, preparation embodiment
Embodiment 1
(1) extracting honeysuckle 400g drying was pulverized 20 mesh sieves, dropped in the extraction kettle to extract, and 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 1h gets 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, it is 3000 hollow fiber column ultrafilter that high speed centrifugation, centrifugal liquid are crossed molecular cut off, the NKA-9 macroporous adsorptive resins of having handled well on ultrafiltrate absorption, behind the water elution with 3 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 15g of medicinal residues behind the volatile oil;
(3) extracting honeysuckle 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 Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 15 adds Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain Flos Lonicerae volatile oil clathrate 30g;
(4) prescription of preparation of the present invention is:
Flos Lonicerae volatile oil clathrate 30g, the ethanol extract 15g of medicinal residues behind the extraction volatile oil, baicalin 40g, mannitol 115g;
(5) get above-mentioned clathrate, extract that ethanol extract, baicalin and the mannitol of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, and adds the injection water to ormal weight, add sodium thiosulfate 0.3g, regulate pH value to 6.5-7.5, filtering with microporous membrane, fill, lyophilization, promptly.
Embodiment 2
(1) extracting honeysuckle 400g drying was pulverized 20 mesh sieves, dropped in the extraction kettle to extract, and 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 3h gets 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, it is 3000 hollow fiber column ultrafilter that high speed centrifugation, centrifugal liquid are crossed molecular cut off, the HPD-450 macroporous adsorptive resins of having handled well on ultrafiltrate absorption, 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 20g of medicinal residues behind the volatile oil;
(3) extracting honeysuckle 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 Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 20 adds Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain Flos Lonicerae volatile oil clathrate 50g;
(4) prescription of preparation of the present invention is:
Flos Lonicerae volatile oil clathrate 50g, the ethanol extract 20g of medicinal residues behind the extraction volatile oil, baicalin 40g, lactose 140g;
(5) get above-mentioned clathrate, extract that ethanol extract, baicalin 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 0.25g, regulate pH value to 6.5-7.5, filtering with microporous membrane, fill, lyophilization, promptly.
Embodiment 3
(1) extracting honeysuckle 400g drying was pulverized 20 mesh sieves, dropped in the extraction kettle to extract, and 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 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, it is 3000 hollow fiber column ultrafilter that high speed centrifugation, centrifugal liquid are crossed molecular cut off, the HPD-450 macroporous adsorptive resins of having handled well on ultrafiltrate absorption, behind the water elution with 2 times of column volumes, 3 times of column volumes of reuse, 35% ethanol water eluting is got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract 10g of medicinal residues behind the volatile oil;
(3) extracting honeysuckle 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 Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 15 adds Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain Flos Lonicerae volatile oil clathrate 40g;
(4) prescription of preparation of the present invention is:
Flos Lonicerae volatile oil clathrate 40g, the ethanol extract 10g of medicinal residues behind the extraction volatile oil, baicalin 40g, glucosan 160g;
(5) get above-mentioned clathrate, extract that ethanol extract, baicalin and the glucosan of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, and adds the injection water to ormal weight, add arabo-ascorbic acid 0.25g, regulate pH value to 6.5-7.5, filtering with microporous membrane, fill, lyophilization, promptly.
Embodiment 4
(1) extracting honeysuckle 400g drying was pulverized 20 mesh sieves, dropped in the extraction kettle to extract, and 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 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, it is 3000 hollow fiber column ultrafilter that high speed centrifugation, centrifugal liquid are crossed molecular cut off, the NKA-9 macroporous adsorptive resins of having handled well on ultrafiltrate absorption, behind the water elution with 3 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 12.5g of medicinal residues behind the volatile oil;
(3) extracting honeysuckle 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 Flos Lonicerae volatile oil: the ratio (v/g) of HP-beta-schardinger dextrin-=1: 20 adds Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain Flos Lonicerae volatile oil clathrate 45g;
(4) prescription of preparation of the present invention is:
Flos Lonicerae volatile oil clathrate 45g, the ethanol extract 12.5g of medicinal residues behind the extraction volatile oil, baicalin 40g, mannitol 100g;
(5) get above-mentioned clathrate, extract that ethanol extract, baicalin and the mannitol of medicinal residues mixes behind the volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, and adds the injection water to ormal weight, add sodium thiosulfate 0.2g, regulate pH value to 6.5-7.5, filtering with microporous membrane, fill, lyophilization, promptly.
Claims (8)
1. honey suckle and baikal skullcap root freeze dried injection, it is characterized in that it is to be extracted by Flos Lonicerae volatile oil HP-beta-CD inclusion 3-5 weight portion, Flos Lonicerae that ethanol extract 1.2-2 weight portion, baicalin 4 weight portions and the pharmaceutic adjuvant 10-20 weight portion of medicinal residues is prepared from behind the volatile oil, wherein Flos Lonicerae extracts that the ethanol extract of medicinal residues is 85%-90% in chlorogenic acid content behind the volatile oil.
2. honey suckle and baikal skullcap root freeze dried injection according to claim 1, it is characterized in that this lyophilized injectable powder adopts the volatile oil component in the supercritical carbon dioxide extraction method extraction Flos Lonicerae, carry out enclose with the HP-beta-schardinger dextrin-, medicinal residues reuse alcohol reflux, high speed centrifugation, ultrafiltration also carry out the ethanol extract that separation and purification obtains extracting medicinal residues behind the volatile oil with macroporous resin, the ethanol extract of medicinal residues behind Flos Lonicerae volatile oil clathrate, the extraction volatile oil, baicalin and pharmaceutic adjuvant are mixed with.
3. honey suckle and baikal skullcap root freeze dried injection according to claim 1, its preparation method may further comprise the steps:
(1) extracting honeysuckle drying was pulverized 20 mesh sieves, dropped in the extraction kettle to extract, and 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 Flos Lonicerae volatile oil, and is standby;
(2) 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, it is 3000 hollow fiber column ultrafilter that high speed centrifugation, centrifugal liquid are crossed molecular cut off, 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 35%-45% ethanol water eluting got ethanol elution, concentrating under reduced pressure, drying obtains extracting the ethanol extract of medicinal residues behind the volatile oil;
(3) extracting honeysuckle 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 Flos Lonicerae volatile oil: the ratio of HP-beta-schardinger dextrin-=1: 15-20 (v/g) adds Flos Lonicerae volatile oil, stirs 180 minutes, take out cold preservation 24 hours, sucking filtration, filtering residue room temperature dry 36 hours down obtain the Flos Lonicerae volatile oil clathrate;
(4) ethanol extract, baicalin and the pharmaceutic adjuvant of medicinal residues mixes behind extracting honeysuckle volatile oil clathrate compound, the extraction volatile oil, add the dissolving of injection water, activated carbon adsorption is filtered, and adds the injection water to ormal weight, add antioxidant, regulate pH value to 6.5-7.5, filtering with microporous membrane, fill, lyophilization, promptly.
4. according to claim 1 or 3 described honey suckle and baikal skullcap root freeze dried injections, the lyophilizing filler is a kind of in mannitol or lactose or the glucosan.
5. according to claim 1 or 3 described honey suckle and baikal skullcap root freeze dried injections, antioxidant is a kind of in sodium thiosulfate, sodium ascorbate, the arabo-ascorbic acid.
6. honey suckle and baikal skullcap root freeze dried injection according to claim 3, the extraction temperature of supercritical carbon dioxide extraction are 45 ℃, and pressure is 30MPa, and resolution temperature is 55 ℃, and pressure is 6MPa, and average discharge is 120kg/h, and the extraction time is 1-3h.
7. honey suckle and baikal skullcap root freeze dried injection according to claim 3, wherein macroporous adsorbent resin is NKA-9 or HPD-450 type.
8. honey suckle and baikal skullcap root freeze dried injection according to claim 3, wherein the concentration of alcohol of macroporous adsorbent resin eluting is 39%-41%.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1961888B (en) * | 2005-11-11 | 2010-04-28 | 杭州华东医药集团生物工程研究所有限公司 | Scutellaria baicalensis extract freeze-dried powder injection and preparation method thereof |
| CN101897756A (en) * | 2010-07-08 | 2010-12-01 | 四川升和制药有限公司 | Silver yellow medicinal preparation containing polyethylene glycol 12-hydroxy stearate and preparation method thereof |
| CN1939409B (en) * | 2006-10-23 | 2010-12-15 | 石药集团欧意药业有限公司 | Capsules of honeysuckle flower and coptis and preparation thereof |
| CN112315992A (en) * | 2020-11-18 | 2021-02-05 | 劲牌持正堂药业有限公司 | Preparation method of high-solubility full-ingredient honeysuckle extract |
| PL447670A1 (en) * | 2024-01-31 | 2024-09-23 | Uniwersytet Mikołaja Kopernika W Toruniu | Alcoholic ethanol extract from air-dried Scutellaria baicallensis root for use in preparations increasing bee immunity and combating nosema, alcoholic ethanol extract from air-dried Scutellaria baicallensis root and method of obtaining ethanol extract from air-dried Scutellaria baicallensis root |
| PL447669A1 (en) * | 2024-01-31 | 2024-10-07 | Uniwersytet Mikołaja Kopernika W Toruniu | Alcoholic ethanol extract from fresh freeze-dried Scutellaria baicallensis root for use in preparations increasing the immunity of bees and combating nosema, alcoholic ethanol extract from fresh freeze-dried Scutellaria baicallensis root and method for obtaining alcoholic ethanol extract from fresh freeze-dried Scutellaria baicallensis root |
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2004
- 2004-11-18 CN CN 200410091534 patent/CN1634461A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1961888B (en) * | 2005-11-11 | 2010-04-28 | 杭州华东医药集团生物工程研究所有限公司 | Scutellaria baicalensis extract freeze-dried powder injection and preparation method thereof |
| CN1939409B (en) * | 2006-10-23 | 2010-12-15 | 石药集团欧意药业有限公司 | Capsules of honeysuckle flower and coptis and preparation thereof |
| CN101897756A (en) * | 2010-07-08 | 2010-12-01 | 四川升和制药有限公司 | Silver yellow medicinal preparation containing polyethylene glycol 12-hydroxy stearate and preparation method thereof |
| CN112315992A (en) * | 2020-11-18 | 2021-02-05 | 劲牌持正堂药业有限公司 | Preparation method of high-solubility full-ingredient honeysuckle extract |
| PL447670A1 (en) * | 2024-01-31 | 2024-09-23 | Uniwersytet Mikołaja Kopernika W Toruniu | Alcoholic ethanol extract from air-dried Scutellaria baicallensis root for use in preparations increasing bee immunity and combating nosema, alcoholic ethanol extract from air-dried Scutellaria baicallensis root and method of obtaining ethanol extract from air-dried Scutellaria baicallensis root |
| PL447669A1 (en) * | 2024-01-31 | 2024-10-07 | Uniwersytet Mikołaja Kopernika W Toruniu | Alcoholic ethanol extract from fresh freeze-dried Scutellaria baicallensis root for use in preparations increasing the immunity of bees and combating nosema, alcoholic ethanol extract from fresh freeze-dried Scutellaria baicallensis root and method for obtaining alcoholic ethanol extract from fresh freeze-dried Scutellaria baicallensis root |
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