CN1679546A - Freeze-dried powder injection of andrographolide and preparation thereof - Google Patents
Freeze-dried powder injection of andrographolide and preparation thereof Download PDFInfo
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Abstract
A freeze--dried powder injection of andrographolide is prepared from and regrapholide, hydroxypropyl-beta-cyclodextrin, etc through coating by optimal method.
Description
Affiliated technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of freeze-dried powder injection of andrographolide and preparation method thereof.
Technical background
Herba Andrographis is acanthaceous plant, has heat-clearing toxin-expelling functions, cures mainly dysentery, cold, fever, laryngopharynx swelling and pain, aphtha of the mouth and tongue, carbuncle skin infection.Andrographolide (Andrographolide) is the diterpene ginkgolide that extraction obtains in acanthaceous plant Herba Andrographis Andrographis Paniculata (Burm.f.) NeeS, be the important extract and the effective active components of Chinese medicine medicinal plants Herba Andrographis, have functions such as heat-clearing and toxic substances removing, removing heat from blood detumescence.
Modern pharmacological research shows, andrographolide and derivant thereof are (as the dehydrorographolide succinic acid half-ester, potasium dehydroandrographolisuccinate succinate injection, LIANBIZHI ZHUSHEYE, the clean eye drop of virus, compound Chuanhuning liniment etc.) it is antibiotic to have an anti inflammation and heat resolution, viral infection resisting, antitumor, anti-cardiovascular disease, immunostimulation, effect such as hepatic cholagogic and antifertility, clinical diseases such as upper respiratory tract infection and bacillary dysentery, the clinical bacillary dysentery that also is used for of being used for, enteritis, typhoid fever, respiratory tract infection, the coupler body disease, tuberculosis, leprosy, skin infection, hepatitis, otitis media, pelvic inflammatory disease, chorionic epithelioma, Asia property hydatidiform mole, induced labor, thromboangiitis obliterans etc.Diterpene bicyclic mother nucleus and lactone ring five membered structure thereof are the basic framework of heat-clearing and toxic substances removing in the andrographolide chemical structural formula.Because the andrographolide chemical compound is insoluble in water, the way that all adopts chemical constitution to modify is at present introduced hydrophilic group and is prepared various andrographolide salt prefs.But these medicines have changed the structure of cruel chemical compound in the Herba Andrographis, because of the variation of its structure has reduced the pharmaceutically active effect of andrographolide, and have improved poisonous side effect of medicine; And Herba Andrographis herb crude extract human body direct drug injection, composition is complicated and effectively become the composition bioavailability low.Report is arranged in recent years repeatly, use Herba Andrographis extract preparation (for example Chuanhuning preparation) to produce the report of untoward reaction.The LIANBIZHI ZHUSHEYE of clinical practice (andrographolidum Natrii Bisulfis) is because andrographolidum Natrii Bisulfis has the lactone structure of a diterpene, its aqueous solution is to thermally labile, easily open loop degraded, unstable in storage process, pH value can obviously reduce after placement a period of time, and content descends to some extent simultaneously, thereby affect the treatment, the quality of clinical application is affected, makes troubles for the preparation and the storage of medicine, also there is inconvenience in aqueous solution transportation simultaneously.
Patent (application number 200310111332 and application number 200310112722) discloses the preparation method of andrographolidum Natrii Bisulfis injectable powder respectively, above patent adopts common process that andrographolidum Natrii Bisulfis is prepared into the powder pin, there is not creativeness, though improved stability to a certain extent, but because the addition compound product that andrographolidum Natrii Bisulfis is, therefore compare its activity, curative effect, toxic and side effects has certain influence, and does not have essence to change to the stability of lactonic ring with andrographolide.Patent (application number 03111128) discloses a kind of method and preparation thereof of cyclodextrin inclusion compound andrographolide, use ultrasonic method enclose andrographolide in this patent, the andrographolide consumption is 3-8g, cyclodextrin or derivant consumption are 10-80g, this range spans is bigger, the concrete effect of its enclose is also unknown, and has stronger selectivity when studies show that different rings dextrin derivative enclose different pharmaceutical, consumption also has marked difference, and above consumption does not obtain imbody yet in description, HP-consumption during enclose is an andrographolide as can be seen from the embodiment of this patent: HP-is 1: 3 to 1: 5, but consumption enclose effect when this proportion is poor when studies show that with HP-enclose medicine, inclusion rate and utilization ratio of drug are all extremely low, and from this patent working example 1 can know this patent semi-finished product andrographolide clathrate with solution state directly and adjuvant be mixed with lyophilized powder, obviously this does not meet the basic demand of Chinese medicine and lyophilized formulations new drug research, is unfavorable for quality control.
Summary of the invention
For these reasons, the present invention is through research repeatedly, the preferred best approach and the consumption of andrographolide with the HP-enclose, the andrographolide clathrate is mixed with into lyophilized injectable powder with pharmaceutic adjuvant, freeze-dried powder injection of andrographolide of the present invention has good stability, dissolubility, and pharmacological evaluation shows that the present invention has better pharmacological action.
The object of the present invention is to provide a kind of good stability, freeze-dried powder injection of andrographolide evident in efficacy.
The present invention also aims to provide the preparation method of this lyophilized injectable powder.
The present invention is achieved through the following technical solutions.
One, process recipes
(1) gets andrographolide, carry out enclose with HP-: take by weighing HP-, the adding distil water heating for dissolving with saturated water solution method, be made into saturated solution, be chilled to room temperature, in andrographolide: the ratio of HP-=1: 10-18 adds andrographolide, the limit edged stirs, mixing time 2-5 hour, temperature was controlled below 45 ℃, leaves standstill, centrifugal, filter, cold drying obtains the andrographolide clathrate;
(2) the prescription weight portion of preparation of the present invention consists of: the andrographolide clathrate is 29-60 part, and pharmaceutic adjuvant is 2-11 part;
(3) get andrographolide clathrate and pharmaceutic adjuvant mixing according to preparation prescription of the present invention, add the dissolving of injection water fully, the adjusting pH value is 4-6, with the membrane filtration of 0.22um, and filtrate injection cillin bottle, lyophilization obtains freeze-dried powder injection of andrographolide.
HP-is to use increasingly extensive a kind of derivant in recent years, relatively having water solublity with the commonly used beta-schardinger dextrin-of tradition significantly improves, Heat stability is good, the significantly reduced advantage of haemolysis, and can be used for ejection preparation, the present invention has carried out enclose with water solublity and the relatively poor andrographolide of stability with HP-, can significantly strengthen stability of drug, improve medicine dissolubility in water, be beneficial to the preparation lyophilized injectable powder, adopt its drug action of lyophilized injectable powder of preparation technology's preparation of the present invention also to be significantly improved.
Two, the selection of inclusion method
Get andrographolide respectively and adopt inclusion method commonly used: saturated water solution method, ultrasonic method, spray drying method compare experiment, and measure the inclusion rate of each group experiment respectively.
Saturated water solution method: HP-is dissolved in the distilled water, and heating for dissolving is made saturated solution, be chilled to room temperature, get andrographolide 4g and add dissolve with ethanol, in andrographolide: in the saturated solution that the ratio of HP-(1: 10) adds, the limit edged stirs, mixing time 4 hours, temperature control is left standstill below 45 ℃, filters, cold drying, promptly.
Polishing: get 5 times of water gagings and mix, again 4g in the Herba Andrographis is dissolved in the ethanol, add in the mixture, in grinder, fully ground 5 hours with HP-40g, cold drying, promptly.
Supercritical ultrasonics technology (with reference to number of patent application 03111128 disclosed method); With the alcoholic solution of distilled water compound concentration 40-60%, andrographolide 4g is joined in the alcoholic solution, be heated to 60-75 ℃, make it dissolving; Join in the andrographolide alcoholic solution after the dissolving of HP-40g and distilled water for injection, move in the supersonic generator sonic oscillation 30-45 minute, the control temperature leaves standstill below 45 ℃, cold drying, promptly.
Spray drying method: 40g is soluble in water with HP-, heating for dissolving becomes solution, is chilled to room temperature, gets andrographolide 4g and adds dissolve with ethanol, in andrographolide: in the HP-saturated solution that the ratio of HP-(1: 10) is added to, the limit edged stirs, and stirs after 0.5 hour, carries out spray drying, the spray drying condition is: intake air temperature: 170 ℃～180 ℃, air outlet temperature: 70～80C, pressure: 0.04-0.05MPa, promptly.
Measure the inclusion rate of above four kinds of method gained andrographolide clathrates respectively, the results are shown in Table 1.
Table 1 distinct methods inclusion rate relatively
| Group | Inclusion rate (%) |
| Saturated water solution method polishing ultrasonic method spray drying method | ????88.2 ????75.0 ????78.3 ????82.5 |
By above result of the test as can be known.More than in four kinds of methods under the identical situation of Subjective and Objective ratio, inclusion rate is not quite similar, and is the highest with the saturated water solution method inclusion rate, illustrates that andrographolide is better with saturated water solution method enclose effect.
Three, clathrate process HP-optimum amount determines
In order further to screen the optimum amount of HP-enclose of the present invention, with following EXPERIMENTAL DESIGN the clathrate process optimum amount has been carried out further determining with saturated water solution method according to above-mentioned test, measure inclusion rate and andrographolide utilization rate respectively, the results are shown in Table 2.
Andrographolide assay method reference literature method (Fu Xintong, Zhou Furong, Zhang Limin.The content of andrographolide in the high effective liquid chromatography for measuring preparation.CHINA JOURNAL OF CHINESE MATERIA MEDICA, 1995,20 (6): 351-352) carry out.
The different HP-consumption of table 2 enclose effect relatively
| Andrographolide: HP- | Inclusion rate (%) | Andrographolide utilization rate (%) |
| ???????????1∶3 ???????????1∶5 ???????????1∶8 ???????????1∶10 ???????????1∶12 ???????????1∶15 ???????????1∶18 ???????????1∶20 ???????????1∶25 ???????????1∶30 | ????60.3 ????67.2 ????75.4 ????91.2 ????92.4 ????93.8 ????92.5 ????85.0 ????82.0 ????81.7 | ?????56.0 ?????64.4 ?????71.7 ?????86.9 ?????88.5 ?????89.2 ?????88.7 ?????80.0 ?????77.3 ?????77.1 |
By above result of the test as can be known, HP-enclose andrographolide has very strong selectivity, the input amount of object has bigger influence to inclusion rate, andrographolide wherein: the HP-ratio is to significantly improve than 1: 8 o'clock inclusion rate in 1: 10 o'clock, continue increase ratio to 1: at 18 o'clock, inclusion rate is all more than 90%, and it is more stable, and: the HP-ratio increases to 1: 20 back inclusion rate and reduces on the contrary, and the optimum amount when therefore andrographolide of the present invention being described with the HP-enclose is 1: 10 to 1: 18.
Four, stability experiment
Experiment medicine: lyophilized injectable powder of the present invention (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides); Commercially available LIANBIZHI ZHUSHEYE (Wuxi Shanhe Medicine Industry Co., Ltd).
Experimental technique: adopt the accelerated tests method to carry out stability experiment, commercially available LIANBIZHI ZHUSHEYE and freeze-dried powder injection of andrographolide of the present invention are placed on 37 ℃ of room temperatures, relative humidity is 75% condition preservation, measures the content and the comparison in 0 month together of the andrographolidum Natrii Bisulfis and the freeze-dried powder injection of andrographolide andrographolide of the present invention of LIANBIZHI ZHUSHEYE respectively.Experimental result sees Table 3
The changes of contents of table 3 accelerated stability test
| Group | Content drop-out value (%) | |||
| January | February | March | June | |
| Commercially available LIANBIZHI ZHUSHEYE freeze-dried powder injection of andrographolide of the present invention | ??1.12 ??0.25 | ??1.80 ??0.53 | ??3.16 ??0.87 | ????5.02 ????1.39 |
Conclusion: test content that we can observe freeze-dried powder injection of andrographolide of the present invention by above-mentioned accelerated stability and change in 6 months less at accelerated stability test, commercially available LIANBIZHI ZHUSHEYE content bigger variation is arranged, prove absolutely that andrographolide in the andrographolide injectable powder of the present invention through better with the product stability after the sodium sulfite addition than andrographolide behind the enclose, proves absolutely meaning of the present invention.
Five, pharmacology embodiment
Trial drug: freeze-dried powder injection of andrographolide of the present invention (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides); LIANBIZHI ZHUSHEYE (Wuxi Shanhe Medicine Industry Co., Ltd); Potasium dehydroandrographolisuccinate succinate injection (Wu Liang Ye Group, Yibin Pharmaceutical Co.,Ltd., Yibin,Sichuan).
1. antibacterial action
Experimental technique: the filter paper method is measured bacteriostasis: the filter paper of cut-off footpath 6mm, and to put into drug solution (sample is made into identical clinical application concentration) 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 ℃ the interior 48h of cultivation of biochemical incubator, the inhibition zone size of filter paper behind mensuration 24h, the 48h, and relatively fungistatic effect sees Table 4.
Table 4 pair inhibition effect for the examination strain
| For the examination strain | LIANBIZHI ZHUSHEYE | Potasium dehydroandrographolisuccinate succinate injection | Herba Andrographis lyophilized injectable powder of the present invention |
| Bacteriostatic diameter (mm) 24h 48h | Bacteriostatic diameter (mm) 24h 48h | Bacteriostatic diameter (mm) 24h 48h | |
| Staphylococcus aureus Staphylococcus albus escherichia coli dysentery bacterium pneumobacillus | 9.0????9.0 10.2???10.5 8.0????8.5 5.0????5.0 6.5????5.5 | 9.0?????9.0 10.2????10.5 8.0?????8.5 5.0?????5.0 6.5?????6.0 | ?9.7??????9.5 ?11.0?????11.5 ?8.5??????9.0 ?6.5??????6.5 ?7.5??????7.5 |
Conclusion: show that by above-mentioned pharmacological evaluation freeze-dried powder injection of andrographolide of the present invention and LIANBIZHI ZHUSHEYE, potasium dehydroandrographolisuccinate succinate injection relatively have better antibacterial action.
2. antivirus action
Experimental technique: get 120 of mices, male and female half and half, be divided into 4 groups at random, every group 30, after mice is anaesthetized with ether is slight, it is 1: 320 pneumonia of mice virus 0.04ml that every Mus collunarium gives titre, next day intraperitoneal injection, freeze-dried powder injection of andrographolide group dosage of the present invention is 50mg/kg, LIANBIZHI ZHUSHEYE group dosage is: 100mg/kg, potasium dehydroandrographolisuccinate succinate injection group dosage is 50 mg/kg, the normal saline group is with 0.2ml normal saline lumbar injection, and successive administration 7d observes 20d, record animal dead number the results are shown in Table 5.
The influence of table 5 pair mouse infection pneumonia mortality rate
| Group | Death toll | Mortality rate |
| Normal saline group LIANBIZHI ZHUSHEYE group potasium dehydroandrographolisuccinate succinate injection group freeze-dried powder injection of andrographolide group of the present invention | ??27 ??21 ??20 ??16 | ??90％ ??70％ ??66.67％ ??53.33％ |
Conclusion: above The pharmacological results shows that freeze-dried powder injection of andrographolide of the present invention can significantly reduce mouse infection pneumonitis virus mortality rate, and has than LIANBIZHI ZHUSHEYE, the better pharmacological action of potasium dehydroandrographolisuccinate succinate injection.
3. separate heat test:
Experimental technique: choose 50 of healthy new zealand white rabbits, body weight is 1000-1250g, male and female half and half, the same day was surveyed the anus temperature 3 times in experiment, averaged as normal body temperature, then in back subcutaneous injection 5% sterilised yeast suspension 5ml/kg, select 40 of the New Zealand white rabbit of body temperature rise more than 0.8 ℃ after 5 hours, be divided into the normal saline group at random, LIANBIZHI ZHUSHEYE, potasium dehydroandrographolisuccinate succinate injection, freeze-dried powder injection of andrographolide group of the present invention, 10 of every treated animals.Administration group intraperitoneal injection, freeze-dried powder injection of andrographolide group dosage of the present invention is 50mg/kg, LIANBIZHI ZHUSHEYE group dosage is 100mg/kg, and potasium dehydroandrographolisuccinate succinate injection group dosage is 50mg/kg: the normal saline group gives 0.2ml normal saline lumbar injection.Respectively surveyed body temperature 1 time respectively at 1,2,3 hour after the administration, relatively the difference of each treated animal body temperature drop-out value the results are shown in Table 6.
The refrigeration function of table 6 pair New Zealand white rabbit
| Group | Normal body temperature (℃) | 5h body temperature after the pyrogenicity (℃) | The body temperature drop-out value (℃) 123 |
| Normal saline group LIANBIZHI ZHUSHEYE group potasium dehydroandrographolisuccinate succinate injection group freeze-dried powder injection of andrographolide of the present invention | ?39.20±0.15 ?39.24±0.17 ?39.21±0.15 ?39.25±0.16 | ??40.21±0.35 ??40.32.±0.36 ??40.30±0.35 ??40.34±0.30 | ?0.05±0.07???0.15±0.10????0.33±0.16 ?0.23±0.13???0.53±0.15 *??0.68±0.17 *?0.24±0.15???0.52±0.16 *??0.67±0.14 *?0.55±0.18 *?0.92±0.12 **?0.99±0.20 ** |
Annotate: compare with the normal saline group
*P＜0.05,
*P＜0.01
Conclusion: above pharmacological testing shows that freeze-dried powder injection of andrographolide of the present invention has the better antipyretic effect, and stronger than LIANBIZHI ZHUSHEYE, potasium dehydroandrographolisuccinate succinate injection effect.
4. antiinflammatory test;
Experimental technique: get 40 of healthy mices, male and female half and half, be divided into 4 groups at random, be divided into the normal saline group, the LIANBIZHI ZHUSHEYE group, the potasium dehydroandrographolisuccinate succinate injection group, freeze-dried powder injection of andrographolide group of the present invention, administration group intraperitoneal injection, freeze-dried powder injection of andrographolide group dosage of the present invention is 50mg/kg, LIANBIZHI ZHUSHEYE group dosage is 100mg/kg, potasium dehydroandrographolisuccinate succinate injection group dosage is 50mg/kg,: the normal saline group gives 0.2ml normal saline lumbar injection, administration every day 1 time, totally 7 days, last administration 1h, with the about 5s of dimethylbenzene cotton balls contact mice left side ear, take off cervical vertebra after 15 minutes and put to death mice, cut ears, punching is weighed, calculate the ear swelling degree of every group of mice, and ask suppression ratio, the results are shown in Table 7.
The influence of table 7 xylol induced mice ear swelling
| Group | Number of animals (only) | Swelling degree (mg) | Suppression ratio (%) |
| Normal saline group LIANBIZHI ZHUSHEYE group potasium dehydroandrographolisuccinate succinate injection group freeze-dried powder injection of andrographolide of the present invention | ????10 ????10 ????10 ????10 | ??10.2±1.3 ??7.4±0.8 *??7.5±0.7 *??6.0±0.5 ** | ????27.5 ????26.5 ????41.2 |
Annotate: compare with the normal saline group
*P＜0.05,
*P＜0.01
Conclusion: above pharmacological testing shows that freeze-dried powder injection of andrographolide of the present invention has antiinflammatory action preferably, and stronger than LIANBIZHI ZHUSHEYE, potasium dehydroandrographolisuccinate succinate injection effect.
Six, preparation embodiment
Embodiment 1
(1) gets andrographolide 50g, adopt saturated water solution method to carry out enclose: to take by weighing HP-, the adding distil water heating for dissolving with HP-, be made into saturated solution, be chilled to room temperature, according to andrographolide: the ratio of HP-=1: 10 adds andrographolide, the limit edged stirs, mixing time 2 hours, temperature is controlled below 45 ℃, leaves standstill, centrifugal, filter, cold drying obtains andrographolide clathrate 590g;
(2) prescription of preparation of the present invention is: andrographolide clathrate 590g, mannitol are 60g.
(3) get andrographolide clathrate and pharmaceutic adjuvant and mix, add the dissolving of injection water fully, the adjusting pH value is 4-6, and with the membrane filtration of 0.22um, filtrate is injected cillin bottle, and lyophilization obtains 1000 bottles of freeze-dried powder injection of andrographolide.
Embodiment 2
(1) gets andrographolide 40g, adopt saturated water solution method to carry out enclose: to take by weighing HP-, the adding distil water heating for dissolving with HP-, be made into saturated solution, be chilled to room temperature, according to andrographolide: the ratio of HP-=1: 15 adds andrographolide, the limit edged stirs, mixing time 3 hours, temperature is controlled below 45 ℃, leaves standstill, centrifugal, filter, cold drying obtains andrographolide clathrate 600g;
(2) prescription of preparation of the present invention is: andrographolide clathrate 600g, lactose 50g;
(3) get andrographolide clathrate and lactose and mix, add the dissolving of injection water fully, the adjusting pH value is 4-6, and with the membrane filtration of 0.22um, filtrate is injected cillin bottle, and lyophilization obtains 1000 bottles of freeze-dried powder injection of andrographolide.
Embodiment 3
(1) gets andrographolide 30g, adopt saturated water solution method to carry out enclose: to take by weighing HP-, the adding distil water heating for dissolving with HP-, be made into saturated solution, be chilled to room temperature, according to andrographolide: the ratio of HP-=1: 18 adds andrographolide, the limit edged stirs, mixing time 4 hours, temperature is controlled below 45 ℃, leaves standstill, centrifugal, filter, cold drying obtains andrographolide clathrate 550g;
(2) prescription of preparation of the present invention is: andrographolide clathrate 550g, levan 50g;
(3) get andrographolide clathrate and levan and mix, add the dissolving of injection water fully, the adjusting pH value is 4-6, and with the membrane filtration of 0.22um, filtrate is injected cillin bottle, and lyophilization obtains 1000 bottles of freeze-dried powder injection of andrographolide.
Embodiment 4
(1) gets andrographolide 30g, adopt saturated water solution method to carry out enclose: to take by weighing HP-, the adding distil water heating for dissolving with HP-, be made into saturated solution, be chilled to room temperature, according to andrographolide: the ratio of HP-=1: 10 adds andrographolide, the limit edged stirs, mixing time 5 hours, temperature is controlled below 45 ℃, leaves standstill, centrifugal, filter, cold drying obtains andrographolide clathrate 290g;
(2) prescription of preparation of the present invention is: andrographolide clathrate 290g, mannitol 80g, dextran 30g;
(3) get andrographolide clathrate and mannitol, dextran mixing, add the dissolving of injection water fully, the adjusting pH value is 4-6, with the membrane filtration of 0.22um, and filtrate injection cillin bottle, lyophilization obtains 1000 bottles of freeze-dried powder injection of andrographolide.
Embodiment 5
(1) gets andrographolide 40g, adopt saturated water solution method to carry out enclose: to take by weighing HP-, the adding distil water heating for dissolving with HP-, be made into saturated solution, be chilled to room temperature, according to andrographolide: the ratio of HP-=1: 10 adds andrographolide, the limit edged stirs, mixing time 3 hours, temperature is controlled below 45 ℃, leaves standstill, centrifugal, filter, cold drying obtains andrographolide clathrate 410g;
(2) prescription of preparation of the present invention is: andrographolide clathrate 410g, glucose 90g;
(3) get andrographolide clathrate and glucose and mix, add the dissolving of injection water fully, the adjusting pH value is 4-6, and with the membrane filtration of 0.22um, filtrate is injected cillin bottle, and lyophilization obtains 1000 bottles of freeze-dried powder injection of andrographolide.
Embodiment 6
(1) gets andrographolide 40g, adopt saturated water solution method to carry out enclose: to take by weighing HP-, the adding distil water heating for dissolving with HP-, be made into saturated solution, be chilled to room temperature, according to andrographolide: the ratio of HP-=1: 12 adds andrographolide, the limit edged stirs, mixing time 4 hours, temperature is controlled below 45 ℃, leaves standstill, centrifugal, filter, cold drying obtains andrographolide clathrate 480g;
(2) prescription of preparation of the present invention is: andrographolide clathrate 480g, mannitol 20g;
(3) get andrographolide clathrate and mannitol mixing according to preparation prescription of the present invention, add the dissolving of injection water fully, the adjusting pH value is 4-6, membrane filtration with 0.22um, filtrate is injected cillin bottle, and lyophilization obtains 1000 bottles of freeze-dried powder injection of andrographolide.
Claims (3)
1. a freeze-dried powder injection of andrographolide is characterized in that the preparation prescription weight portion consists of: andrographolide clathrate 29-60 part, pharmaceutic adjuvant 2-11 part.
2. the preparation method of a kind of freeze-dried powder injection of andrographolide according to claim 1, its feature may further comprise the steps:
(1) gets andrographolide, adopt saturated water solution method: take by weighing HP-, the adding distil water heating for dissolving, be made into saturated solution, be chilled to room temperature, according to andrographolide: the ratio of HP-=1: 10-18 adds andrographolide, the limit edged stirs, mixing time 2-5 hour, temperature was controlled below 45 ℃, leaves standstill, centrifugal, filter, cold drying obtains the andrographolide clathrate;
(2) get andrographolide clathrate and pharmaceutic adjuvant mixing by preparation prescription of the present invention, add the dissolving of injection water fully, the adjusting pH value is 4-6, with the membrane filtration of 0.22um, and filtrate injection cillin bottle, lyophilization obtains freeze-dried powder injection of andrographolide.
3. a kind of freeze-dried powder injection of andrographolide according to claim 1 is characterized in that: the ratio that the andrographolide clathrate carries out enclose with HP-is an andrographolide: HP-=1: 10-18.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102343096A (en) * | 2010-07-26 | 2012-02-08 | 香港城市大学 | Andrographolide cyclodextrin inclusion compound, preparation method and application thereof |
| CN102657673A (en) * | 2012-05-29 | 2012-09-12 | 海南卫康制药(潜山)有限公司 | Kalii dehydrographolidi succinas freeze-dried powder compound for injection and preparation method thereof |
| EP3912633A1 (en) * | 2020-05-16 | 2021-11-24 | Ambe Phytoextracts Pvt. Ltd. | Bioactive formulation and method for preparation thereof |
-
2005
- 2005-02-04 CN CN 200510004895 patent/CN1286457C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102343096A (en) * | 2010-07-26 | 2012-02-08 | 香港城市大学 | Andrographolide cyclodextrin inclusion compound, preparation method and application thereof |
| CN102657673A (en) * | 2012-05-29 | 2012-09-12 | 海南卫康制药(潜山)有限公司 | Kalii dehydrographolidi succinas freeze-dried powder compound for injection and preparation method thereof |
| EP3912633A1 (en) * | 2020-05-16 | 2021-11-24 | Ambe Phytoextracts Pvt. Ltd. | Bioactive formulation and method for preparation thereof |
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| CN1286457C (en) | 2006-11-29 |
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