CN1283500A - Freeze-dried 'Shenmai' powder for injection and its preparing process - Google Patents
Freeze-dried 'Shenmai' powder for injection and its preparing process Download PDFInfo
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- CN1283500A CN1283500A CN 99115061 CN99115061A CN1283500A CN 1283500 A CN1283500 A CN 1283500A CN 99115061 CN99115061 CN 99115061 CN 99115061 A CN99115061 A CN 99115061A CN 1283500 A CN1283500 A CN 1283500A
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- injection
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- radix ophiopogonis
- radix ginseng
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Abstract
A freeze-dried "Shenmai" powder for injection is prepared from red ginseng and ophiopogon root through extracting active components in water, removing impurities by macroreticular resin adsorption, decolouring, filter, drying to obtain solid extract, proportional mixing, preparing solution, and freeze drying.
Description
The invention belongs to pharmaceutical field, relate to a kind of effective site of extracting with plant amedica Radix Ginseng Rubra and Radix Ophiopogonis and add the new preparation method of freeze-dried ' Shenmai ' powder for injection that suitable vehicle is formed.
The prescription of SHENMAI ZHUSHEJI derives from the bright record of Ming Dynasty Qin Jing " Rhizoma Zingiberis Recens drink " ancient prescription, is formed by the Chinese medicine equivalent prescription of distinguishing the flavor of Radix Ginseng Rubra, Radix Ophiopogonis two.The Radix Ginseng Rubra sweet and slightly bitter taste, slightly warm in nature is gone into spleen, lung, the energy strongly invigorating primordial QI, invigorating the spleen and replenishing QI promotes the production of body fluid, the mind calming and mentality promoting; Radix Ophiopogonis bitter in the mouth, little hardship, cold nature, GUIXIN, lung, stomach three warps can lung moistening clear away heart-fire, nourishing the stomach to promote the production of body fluid.Two medicines share has strongly invigorating primordial QI, supplementing QI to prevent collapse, the effect that foster essence is promoted the production of body fluid.SHENMAI ZHUSHEYE has been widely used in the chemotherapeutic sensitivity attenuation of clinical treatment cardiovascular, respiratory system disease, malignant tumor, the immunostimulant of peritoneal dialysis etc.Yet said preparation contains impurity such as a large amount of pigments, is yellowish-brown liquid, and zest is big during injection, and the effective ingredient Saponin is unstable facile hydrolysis in water, often makes preparation produce precipitation and muddy, the preparation quality standard imperfection, and the control of product quality difficulty is big.CN1086728A relates to the patent of a piece " red ginseng and tuber of dwarf lily turf powder injection and preparation method thereof ", CN1122704A relates to the patent of a piece " frozen powder for injection containing ginseng extract ", ethanol extraction is all adopted in the extraction of medical material, the lixiviating solution color is dark, impurity especially oil-soluble impurities is many, and the purification difficulty is big, and lixiviating solution is not purified or only adopt remove impurity with active carbon, end product is more assorted, directly influences pharmaceutical effectiveness and product stability etc.
The object of the present invention is to provide that a kind of preparation technology is more advanced, more science, quality are more controlled for proportioning, by the preparation method of Radix Ginseng Rubra and the freeze-dried ' Shenmai ' powder for injection that Radix Ophiopogonis, effective site was formed.It is characterized in that adopting respectively water extraction extract Radix Ginseng Rubra and Radix Ophiopogonis effective ingredient, with macroporous resin adsorption impurity and with the decolorizing resin decolouring after multistep is filtered, dry solid extract contains Radix Ginseng total saponins and ophiopogon root total saponin 〉=87% respectively.With Radix Ginseng Rubra effective site 10-20g, Radix Ophiopogonis, effective site 1.0-2.0g added injection skeleton agent I 40-60g, injection skeleton agent II 40-60g, with water for injection 500-1000ml wiring solution-forming, filter, be sub-packed in cillin bottle, frozen drying 26-28 hour, encapsulate under the aseptic condition.
The preparation technology of freeze-dried ' Shenmai ' powder for injection of the present invention is as follows:
One, medical material pre-treatment
Medical material Radix Ginseng Rubra, Radix Ophiopogonis are respectively through choosing, clean, dry, be ground into lamellar or graininess.
Two, extract
1, Radix Ginseng extracts:
Take by weighing and kept 2 hours at 80-90 ℃ after a certain amount of Radix Ginseng Rubra adds 10-20 water boil doubly, filter, medicinal residues kept 1.5 hours at 80-90 ℃ after adding 10-20 water boil doubly, filter, medicinal residues kept 1 hour at 80-90 ℃ after adding 10-20 water boil doubly again, filter, merging filtrate, the speed heart disgorging of wandering about as a refugee gets ginseng aqueous extract.
2, extract Radix Ophiopogonis:
Kept 2 hours at 80-90 ℃ after taking by weighing the water boil that adds 10-20 times a certain amount of Radix Ophiopogonis, filter, medicinal residues kept 1.5 hours at 80-90 ℃ after adding 10-20 water boil doubly, filtration, and medicinal residues kept 1 hour at 80-90 ℃ after adding 10-20 water boil doubly again, filtered.Merge three times filtrate, centrifugal disgorging promptly gets water extract Radix Ophiopogonis.
Three, purification remove impurity
1, the purification of ginseng aqueous extract
Ginseng aqueous extract is regulated pH8.5-9.5 with the 10M sodium hydroxide, at the uniform velocity by the adsorbent resin chromatographic column, after absorption finishes, be washed till colourless with 1% sodium hydroxide, when being washed till pH neutrality with water recently distilled then, use the 75%-85% ethanol elution, to there not being the Saponin reaction, the ethanol liquid behind the eluting is at the uniform velocity crossed refining decolorizing resin chromatographic column, collecting effluent left standstill 12-24 hour, filter, the decompression thin film concentration filters to there not being ethanol, obtain transparent light yellow red ginseng extract, lyophilization under the aseptic condition gets Radix Ginseng Rubra effective site dry extract, ginsenoside content 〉=87%.
2, Radix Ophiopogonis the water extract purification
Radix Ophiopogonis, the water extract was regulated pH8.5-9.5 with the 10M sodium hydroxide, at the uniform velocity by the adsorbent resin chromatographic column, filter, colourless with 1% caustic washing chromatographic column to chromatographic solution, use distilled water then instead and be washed till pH and be neutrality, react to no Saponin with the 75%-85% ethanol elution, ethanol elution is collected the ethanol liquid that flows through at the uniform velocity by the decolorizing resin post, leaves standstill 24-48 hour, filter, be evaporated to no ethanol.Filter, obtain transparent light yellow Radix Ophiopogonis extract, lyophilization under the aseptic condition, Radix Ophiopogonis the live part dry extract, Radix Ophiopogonis saponin content 〉=87%.
Four, freeze-dried ' Shenmai ' powder for injection preparation
1, prescription:
Radix Ginseng effective part extract 10-20g;
Radix Ophiopogonis effective part extract 1.0-2.0g;
Injection skeleton agent I 40-60g;
Injection skeleton agent II 40-60g;
Water for injection adds to 500-1000ml.
2, method for making:
The indoor injection skeleton agent I 40-60g that takes by weighing in the sterile working, injection skeleton agent II 40-60g puts in the sterility container, add injection water 450ml, stirring makes dissolving, add 10-20g Radix Ginseng Rubra effective part extract and 1.0-2.0g effective part extract Radix Ophiopogonis again, add water and complement to 500-1000ml, be stirred to whole dissolvings gently, under positive pressure, micropore filter filtering liquid medicine with two polyphones, gained sterile liquid medicine every bottled amount 1ml of 10ml cillin bottle or the every bottled amount 0.5ml of 5ml cillin bottle, frozen drying 26-28 hour, under aseptic condition, encapsulate.
The process conditions screening
One, Radix Ginseng Rubra live part extracting condition screening
Bibliographical information adopts the alcohol reflux lixiviate as the ginsenoside of Radix Ginseng Rubra live part.Extracting main weak point in this way is: the lixiviating solution color is dark, and impurity especially oil-soluble impurities is many, and the purification difficulty is big, technology relative complex, cost height.For this reason, this test compares research to the best extracting condition of Radix Ginseng Rubra live part, now is summarized as follows:
Sample preparation:
Radix Ginseng Rubra is put in 80 ℃ of baking ovens and is dried by the fire 12hr, pulverizes with pulverizer, crosses 20 mesh sieves.Alcohol reflux lixiviate Radix Ginseng Rubra Saponin: extract the Radix Ginseng Rubra Saponin according to " Sichuan Province's drug standard " 186 pages of SHENMAI ZHUSHEYE method for making alcohol leaching.Specific practice is: claim the 100g red ginseng powder to place flask, add ethanol 300ml and soaked 72 hours, filter filtrate for later use.Medicinal residues add 300ml ethanol, put in the water-bath backflow lixiviate three times, each 2 hours.Saponin content is surveyed in the sampling of each time extracting solution.
Decocting in water lixiviate Radix Ginseng Rubra Saponin: claim the 100g red ginseng powder, place flask, add the 100ml distilled water, boil the back and under 80-90 ℃ of condition, kept 2 hours, filter filtrate for later use.Medicinal residues reuse 100ml distilled water is by aforementioned manner lixiviate twice, and extraction time was respectively 1.5 hours and 1 hour, and filtrate is taken a sample respectively, measures saponin content.
Every processing repeats 3 times, and experimental result (seeing Table 1) shows decocting in water lixiviate Radix Ginseng Rubra Saponin and do not have significant difference with the alcohol reflux lixiviate, only a little less than ethanol extraction.
Table 1 extracting condition influences Radix Ginseng Rubra Saponin extraction rate
| The lixiviate mode | Each time extraction rate: 1 | ????2 | ????3 | Add up to | Total Saponin (g/100g) |
| Decocting in water lixiviate alcohol reflux | ????51.6％ ????58％ | 26％ 27％ | 18％ 15％ | 95.6％ 100％ | ????1.75 ????1.83 |
But ethanol extraction, cost is much higher, compares, to adopt the decocting in water extraction better.
Two, live part leach extraction method comparative test Radix Ophiopogonis
Bibliographical information, Saponin Radix Ophiopogonis as live part Radix Ophiopogonis, general lixiviate also adopts the alcohol reflux lixiviate with this method lixiviate Saponin Radix Ophiopogonis pigment impurity, and especially oil-soluble impurities is many, and Radix Ophiopogonis, active constituent content itself was just very low in addition, subsequent purification is very difficult, technological operation is complicated, the cost height, for this reason, this experiment is studied live part lixiviate Radix Ophiopogonis optimum condition, and the result is summarized as follows:
To put Radix Ophiopogonis in 60 ℃ of baking ovens and dry by the fire 12hr, pulverizer is ground into coarse powder, crosses 20 mesh sieves, and is standby.
Alcohol reflux lixiviate Saponin Radix Ophiopogonis: claim 100g dry powder Radix Ophiopogonis in clean alembic, add 80% ethanol 500ml, backflow lixiviate 2 hours is filtered standby.Medicinal residues add 80% ethanol 250ml backflow lixiviate secondary, and each time time is 1.5 hours, 1 hour, each sampling survey lixiviating solution saponin content that finishes that refluxes.
Decocting in water lixiviating solution Saponin Radix Ophiopogonis: claim the 100g Radix Ophiopogonis powder, put in the alembic, add 1 liter of distilled water, boil the back and be incubated 2 hours down, filter filtrate for later use at 80-90 ℃.Medicinal residues are with 1 liter of distilled water decocting in water lixiviate secondary, and each time time is 1.5 hours and 1 hour, and saponin content is surveyed in each decocting in water lixiviate sampling that finishes.
Each is handled and repeats 3 times
Result of the test shows that decocting in water lixiviate Saponin Radix Ophiopogonis and alcohol reflux lixiviate Saponin Radix Ophiopogonis do not have significant difference (table 2)
The different lixiviate modes of table 2 are to the influence of Saponin yield Radix Ophiopogonis
| The lixiviate mode | Each time yield | ||||
| ????1 | ????2 | ????3 | Add up to | Total Saponin amount (g) | |
| The lixiviate of decocting in water lixiviate alcohol reflux | 54％ 67％ | 26％ 25％ | 17.6％ ????8％ | ????97.6％ ????100％ | ????0.165 ????0.169 |
Three, Radix Ginseng Rubra, Radix Ophiopogonis, Saponin was refining
Decolorizing resin post control parameter: 25ml alcohol liquid/g decolorizing resin, through after this decolorizing column, Radix Ginseng Rubra, Radix Ophiopogonis, alcohol liquid long-pendingly was respectively 29.5 liters and 28.8 liters, standing over night (12hr), filter with No. 4 glass sand hourglasses, No. 5 broken sand hoppers of reuse filter, till the no alcohol of thin film concentrating under reduced pressure (temperature 80-90 ℃, vacuum 68cm).Under the aseptic condition, No. 5 glass sand hourglasses of reuse filter, and lyophilization obtains the total Saponin 180g of Radix Ginseng Rubra respectively, and Radix Ophiopogonis, Saponin 16.8g and use the alcohol reflux lixiviate, and extracted as stated above, make with extra care the Radix Ginseng Rubra Saponin and Radix Ophiopogonis Saponin must measure and be respectively 176.8g and 15.95g.Be lower than water extraction slightly, main cause is because impurity is many, when refining the Saponin loss amount big due to.The three batches of extractions the results are shown in Table 3, table 4.
The total Saponin of three batches of Radix Ginseng Rubra of table 3 extracts result of the test
| Lot number | Total Saponin (g) | Yield | Purity |
| ?G-9804 ?G-9805 ?G-9806 | ????180.2 ????186.8 ????166.5 | ????1.80％ ????1.87％ ????1.67％ | ????94％ ????92％ ????87％ |
Three crowdes of ginsenosides have carried out an inspection such as haemolysis, pyrogen, microorganism, clarity by requirement under state-promulgated pharmacopoeia " injection " item, the result shows, three batches of total Saponins of Radix Ginseng Rubra are under 5mg/ml concentration, observing did not all have the haemolysis generation in 4 hours, and pyrogen, clarity and microorganism all meet the requirements fully.
Three batches of ophiopogon root total saponins of table 4 extract result of the test
| Lot number | Ophiopogon root total saponin (g) | Yield | Purity |
| ????R-9804 ????R-9805 ????R-9806 | ????16.8 ????16.4 ????16.8 | ????1.68‰ ????1.64‰ ????1.68‰ | ????94％ ????92％ ????91％ |
Above-mentioned three batches Radix Ophiopogonis Saponin by state-promulgated pharmacopoeia " injection " down a requirement carried out haemolysis, pyrogen, an inspection such as microorganism, clarity, the result shows: three batches Radix Ophiopogonis Saponin under 2.5mg/ml concentration, observing did not all have the haemolysis generation in 4 hours, and pyrogen, clarity and microorganism all meet the requirements fully.
Four, freeze-dried ' Shenmai ' powder for injection quality examination
1000 totally three batches of trial-production freeze-dried ' Shenmai ' powder for injection.Three batch samples are by 1% sampling rate sampling, and require down to check according to state-promulgated pharmacopoeia " injection ", and the result shows and meets state-promulgated pharmacopoeia " injection " requirement down.See Table 5
Three batches of freeze-dried ' Shenmai ' powder for injection testing results of table 5
| Lot number | Total saponin content * (mg/ bottle) | Chromatographic qualitative is differentiated * * (Saponin speckle number) | Microorganism | Haemolysis | Pyrogen | Clarity |
| 9804 9805 9806 | ????14.2 ????14.6 ????14.6 | ????8 ????8 ????8 | - | - | - | Transparent transparent |
* formulation content is measured and is adopted resin-determination of color
* developing solvent: n-butyl alcohol-ethyl acetate-water (4: 1: 1), carrier: silica gel G.
Claims (2)
1, the new preparation method of a kind of freeze-dried ' Shenmai ' powder for injection, the effective site that it was extracted by Radix Ginseng Rubra and Radix Ophiopogonis adds the Chinese medicine injection lyophilized powder that necessary additional excipient is formed.It is characterized in that:
(1) adopt water extraction to extract Radix Ginseng Rubra and the effective ingredient of Radix Ophiopogonis respectively.
(2) extracting solution decolours after multistep is filtered, the dry solid extract that gets with the macroporous resin adsorption remove impurity and with decolorizing resin, and Radix Ginseng Rubra effective site contains Radix Ginseng total saponins 〉=87%; Radix Ophiopogonis, effective site contained ophiopogon root total saponin 〉=87%.
(3) prescription of freeze-dried ' Shenmai ' powder for injection is formed:
Radix Ginseng Rubra effective site 10-20g;
Radix Ophiopogonis effective site 1.0-2.0g;
Injection skeleton agent I 40-60g;
Injection skeleton agent II 40-60g;
Water for injection 500-1000ml.
2, the method for producing freeze-dried ' Shenmai ' powder for injection according to claim 1 is characterized in that:
(1) Radix Ginseng, Radix Ophiopogonis, medical material was after pre-treatment, add respectively 10-20 doubly water boil and kept 2 hours in 80-90 ℃, filter, extracts 3 times, merging filtrate, centrifugal disgorging respectively must Radix Ginsengs, Radix Ophiopogonis the water extract.
(2) Radix Ginseng, Radix Ophiopogonis, the water extract was regulated pH8.5-9.5 with the 10M sodium hydroxide respectively, at the uniform velocity cross the adsorbent resin chromatographic column, successively with 1% sodium hydroxide, be washed to pH neutrality, to there being the Saponin reaction, at the uniform velocity mistake is made with extra care the decolorizing resin chromatographic column with the 75%-85% ethanol elution, eluent leaves standstill filtration, be evaporated to no ethanol, filter lyophilization under the aseptic condition, respectively Radix Ginseng Rubra and Radix Ophiopogonis effective site solid extract, contain Radix Ginseng, ophiopogon root total saponin respectively 〉=87%.
(3) take by weighing injection skeleton agent I 40-60g under the aseptic condition, injection skeleton agent II 40-60g, Radix Ginseng Rubra effective site 10-20g, Radix Ophiopogonis effective site 1.0-2.0g, add the dissolving of injection water and be diluted to 500-1000ml, the micropore filter filtering liquid medicine with two polyphones is sub-packed in cillin bottle, every bottled amount 1ml of 10ml cillin bottle or the every bottled amount 0.5ml of 5ml cillin bottle, under aseptic condition, encapsulated in frozen drying 26-28 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99115061 CN1283500A (en) | 1999-08-04 | 1999-08-04 | Freeze-dried 'Shenmai' powder for injection and its preparing process |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99115061 CN1283500A (en) | 1999-08-04 | 1999-08-04 | Freeze-dried 'Shenmai' powder for injection and its preparing process |
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| CN1283500A true CN1283500A (en) | 2001-02-14 |
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| CN 99115061 Pending CN1283500A (en) | 1999-08-04 | 1999-08-04 | Freeze-dried 'Shenmai' powder for injection and its preparing process |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106237065A (en) * | 2016-08-25 | 2016-12-21 | 神威药业集团有限公司 | A kind of pharmaceutical composition and preparation method thereof |
| CN106983821A (en) * | 2016-12-16 | 2017-07-28 | 云南腾药制药股份有限公司 | A kind of pharmaceutical composition of strengthen immunity and preparation method thereof, preparation and application |
-
1999
- 1999-08-04 CN CN 99115061 patent/CN1283500A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106237065A (en) * | 2016-08-25 | 2016-12-21 | 神威药业集团有限公司 | A kind of pharmaceutical composition and preparation method thereof |
| CN106983821A (en) * | 2016-12-16 | 2017-07-28 | 云南腾药制药股份有限公司 | A kind of pharmaceutical composition of strengthen immunity and preparation method thereof, preparation and application |
| CN106983821B (en) * | 2016-12-16 | 2018-04-24 | 云南腾药制药股份有限公司 | A kind of pharmaceutical composition of strengthen immunity and preparation method thereof, preparation and application |
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