CN1583131A - Frozen dry powder injection of composite salvia miltiorrhiza and its preparation - Google Patents
Frozen dry powder injection of composite salvia miltiorrhiza and its preparation Download PDFInfo
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- CN1583131A CN1583131A CN 200410046126 CN200410046126A CN1583131A CN 1583131 A CN1583131 A CN 1583131A CN 200410046126 CN200410046126 CN 200410046126 CN 200410046126 A CN200410046126 A CN 200410046126A CN 1583131 A CN1583131 A CN 1583131A
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- 239000007924 injection Substances 0.000 title claims abstract description 57
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- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims abstract description 34
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- Medicines Containing Plant Substances (AREA)
Abstract
A freeze-dried powder injection is prepared through extracting the water-soluble active components from red sage root and notoginseng, including borneol by hydroxypropyl-beta-cyclodextrin, purifying mixing and freeze drying.
Description
Affiliated technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of compound red sage root freezing-dried powder injection and preparation method thereof.
Background technology
Coronary heart disease, angina pectoris are commonly encountered diseases, frequently-occurring disease clinically, in recent years, raising along with people's living standard, the incidence of coronary heart disease age shifts to an earlier date to some extent, add the aging of population structure, its sickness rate is the trend that rises year by year, and the medicine of exploitation treatment cardiovascular and cerebrovascular disease gradually becomes the focus of research.Increasing clinical report shows that Chinese medicine is having a good application prospect aspect treatment coronary heart disease, the angina pectoris, and particularly the few side effects of Chinese medicine is subjected to liking of people day by day.Compound red sage root preparation mainly is made up of Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum, is mainly used in the treatment of cardiovascular disease aspect clinically, has effect preferably, and is fine always as FUFANG DANSHEN DIWAN sales volume on market.In recent years, use clinically based on the preparation of Radix Salviae Miltiorrhizae increasingly extensive, research also deepen continuously.Radix Salviae Miltiorrhizae energy coronary artery dilator, coronary blood flow increasing, decreased heart rate; Platelet aggregation and thrombosis that anti-platelet activating factor is caused; Promote injury of myocardium to recover, increase myocardial contraction, protecting myocardial cell.The pharmacological action of Radix Notoginseng is very extensive, a plurality of systems are all influential to body, it mainly act as hemostasis, blood circulation promoting and blood stasis dispelling, reducing swelling and alleviating pain, Recent study is found again, Radix Notoginseng has effects such as antianginal, treatment cerebrovascular sequelae, anti-hepatitis, particularly contained total saponins constituents in the Radix Notoginseng has physiologically active preferably aspect cardiovascular.Borneolum Syntheticum then has the refreshment of having one's ideas straightened out, the effect of clearing away heat to alleviate pain.Though, widely apply clinically by the injection that Radix Notoginseng and Radix Salviae Miltiorrhizae single medicinal material are made, and multiple dosage form is also arranged clinically by the compound red sage root preparation that three medicines are formed, but all be only limited to oral formulations by the preparation that three medicines are formed, patent CN02158104.5 discloses a kind of compound Salviae Miltiorrhizae solid preparation for the treatment of cardiovascular disease and preparation method thereof, market is not seen to be had by the injection of the above three flavor medicine prescriptions report of lyophilized injectable powder particularly, though the report of relevant FUFANG DANSHEN ZHUSHEYE in the document, as Chinese patent CN98103032, CN02133724, CN02144600, but the compound Salviae Miltiorrhizae of its report is by all being made up of Radix Salviae Miltiorrhizae and Lignum Dalbergiae Odoriferae two flavor medicines, but not by Radix Salviae Miltiorrhizae, Radix Notoginseng, Borneolum Syntheticum three flavor medicines are formed both prescription differences.The compatibility of Chinese medicine compound is used, and can give full play to the characteristics of Chinese medicine multicomponent, many target spots multiaction approach, makes it to have clinically better therapeutic.It is rapid that freeze-dried powder injection has an onset, and therefore the stable again advantage such as transportation storage of being convenient to, further develops particularly its freeze-dried powder dosage form of compound red sage root preparation, will have vast market prospect.
The ejection preparation of being made by Radix Notoginseng and Radix Salviae Miltiorrhizae single medicinal material effective site has more report.Patent CN99106223 discloses the injection of being made by the compound components of panax notoginseng Radix Notoginseng total arasaponins.The cardiovascular main effective ingredient of Treated with Radix Salviae Miltiorrhizae is the soluble salvianolic acid constituents, and patent CN01142288 and patent CN02117923 disclose the preparation method of Radix Salviae Miltiorrhizae total salvianolic acid respectively, all adopts macropore to inhale resin method total salvianolic acid is carried out enrichment and purification.
Patent for compound red sage root preparation, more to its solid dosage forms report, patent CN01136155.7 and patent CN02158104.5 disclose solid dosage forms of this compound preparation and preparation method thereof respectively, and patent CN01133333.2 then discloses slow release and the controlled release form and the preparation method of this compound preparation.Patent CN02157383, CN02157377, CN02157379, CN02157380, CN02157382 then disclose the whole solid dosage forms that consists essentially of compound Salviae Miltiorrhizae, but still do not have the report about the compound red sage root preparation lyophilized injectable powder at present.
Borneolum Syntheticum is a liposoluble constituent, and dissolubility is less in injection, and this also is one of compound red sage root preparation reason of still not having lyophilized injectable powder at present.
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, antibacterial etc. are by the filter membrane detention, thereby reaching separation, purification, spissated new membrane isolation technics with fastest developing speed, can the isolated molecule amount be 1000～1000000 daltonian materials.Use different ultrafilter membranes such as acetate fiber, SPSF, polysulfones, polysulfonamides, polyacrylonitrile, can carry out selectivity to 0.5,1,3,70,000 different molecular quantity of material and hold back.Compare with traditional separation method, have separation process do not have phase transformation, separation efficiency height, need not to add chemical reagent pollution-free, need not to heat, energy consumption is low, mild condition is not destroyed composition, easy to operate, characteristics that flow process is short, can partly replace traditional filtration, absorption and extraction etc. and separate technology, begin to be widely used in biological engineering and the process of Chinese medicine preparation.Can prepare water for injection, transfusion and Chinese medicine injection with ultrafiltration, prepare oral liquid and solid preparation or the like with 5～70,000 molecular weight ultrafilter membranes.In addition,, can also utilize it to remove impurity such as tannin, protein and macromolecular saccharide in the injection, improve the clarity of injection etc. according to the characteristics of ultrafilter membrane.Utilize hyperfiltration technique to prepare injection, can also be used for effectively removing antibacterial and pyrogen, because the mean molecule quantity of pyrogen is about 100,000, the employing molecular cut off is 3000 ultrafilter membrane ultrafiltration, can effectively remove pyrogen.So the present invention adopts hyperfiltration technique in preparation process after, the quality of injection has obtained tangible improvement and raising.
Summary of the invention
The present invention improves the dosage form of FUFANG DANSHEN PIAN (see one one of " pharmacopeia " version in 2000, Chinese Pharmacopoeia Commission compiles), and purpose is to provide that a kind of onset is rapid, dosage form is advanced, the injection use compound red sage root freezing-dried powder injection of preparation stabilization and preparation method thereof.The present invention adopts that decocting cooking method, alcohol extraction are followed the example of, resin adsorption method and ultrafiltration are extracted and purification the Radix Salviae Miltiorrhizae in the compound Salviae Miltiorrhizae tablet preparation, Radix Notoginseng, obtain its water solubility extract, utilize hydroxypropyl (HP-β-CD) Borneolum Syntheticum in the prescription is carried out enclose, solve it and in the injection aqueous solution, dissolved difficult problem, improved the quality and the clinical efficacy of preparation.
The present invention adopts ion-exchange-resin process and macroporous adsorbent resin method that the water soluble ingredient in Radix Salviae Miltiorrhizae and the Radix Notoginseng has been carried out enriching and purifying respectively, and employing ultrafiltration ultrafiltration, the clarity and the pyrogen that have guaranteed injection are qualified, removed the tannin in the red rooted salvia simultaneously, the quality of injection and curative effect are significantly improved.
In addition, aqueous soluble active constituent in the Radix Salviae Miltiorrhizae mostly is aldehydes and acids composition, easy oxidation deterioration in aqueous solution (improve the method [J] of FUFANG DANSHEN ZHUSHEYE stability. Chinese pharmacist, 1998 (3): 143), the present invention is made into lyophilized injectable powder, well solved the problems referred to above, stability of formulation is improved significantly.
The present invention is achieved through the following technical solutions:
1, extraction and preparation
(1) gets the red rooted salvia decoction pieces, decoct with water three times, merge decoction liquor, filter, subsequent filtrate adsorbs with anion exchange resin, wash decontamination reuse sig water eluting earlier with water, to 4-5, be evaporated to relative density is the extractum of 1.20-1.30 (50 ℃) to the alkali eluent with sour adjust pH, adding ethanol makes the alcohol amount of containing reach 60-80%, leave standstill, supernatant reclaims ethanol, and is evaporated to the extractum that relative density is 1.25-1.35 (50 ℃); Extractum adds ethanol while stirring to be made and contains alcohol amount and reach 70-85%, leaves standstill 24 hours, filters, and supernatant reclaims ethanol, and is evaporated to the extractum that relative density is 1.20-1.30 (50 ℃), and vacuum drying gets Radix Salviae Miltiorrhizae extract.
(2) Radix Notoginseng powder is broken into coarse powder, uses the alcohol reflux three times of 50-80% respectively, merge extractive liquid,, filter, after recovery ethanol is extremely most, thin up (extracting solution: medical material=1: 1), high speed centrifugation, supernatant is crossed the macroporous adsorptive resins of having handled well, first washing decontamination with 1 times of resin column volume, the ethanol elution of reuse 50-80%, collect alcohol eluen, reclaim ethanol, being evaporated to relative density is the extractum of 1.20-1.30 (50 ℃), and vacuum drying gets Radix Notoginseng extract.
(3) Borneolum Syntheticum becomes nearly saturated solution standby with anhydrous alcohol solution; Other gets HP-β-CD and adds the injection water and make saturated solution, and Borneolum Syntheticum ethanol liquid slowly is added drop-wise in HP-β-CD saturated solution, and the limit edged stirs, after Borneolum Syntheticum ethanol liquid adds, continue stirred for several hour, mixed liquor cold preservation, filter, the precipitation cold drying gets Borneolum Syntheticum HP-beta-CD inclusion.
(4) get above-mentioned Radix Salviae Miltiorrhizae, Radix Notoginseng extract and add the dissolving of injection water, filter, filtrate is 3000 ultrafilter membrane ultrafiltration with molecular cut off, ultrafiltrate mixes with Borneolum Syntheticum HP-β-CD liquid, adds the lyophilizing excipient, and the accent pH value is 5.0-6.5,80 ℃ of insulations of active carbon with 0.2% 15 minutes, filter, add the injection water, regulate pH value to 8.0 to ormal weight, filter, cool-drying is frozen in fill, promptly.
Big pore adsorption resin of the present invention can be the macroporous resin of nonpolar or low pole, comprises D101 and AB-8 type macroporous resin.
The used freeze-dried excipient of the present invention can be a kind of or two kinds a mixture in mannitol and the lactose.
Test example one: the preliminarily stabilised test of compound lyophilized powder injection
1, test apparatus and material
DL 302 type temperature and humidity regulators (Shanghai Wu's rime hardware factory); HP 1100 chromatograph of liquid (U.S. Anjelen Sci. ﹠ Tech. Inc).Methanol is chromatographically pure, and acetic acid is analytical pure, and water is ultra-pure water; The protocatechualdehyde reference substance is provided by Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
Injection use compound red sage root freezing-dried powder injection and FUFANG DANSHEN ZHUSHEYE (Tianzhijiao Medication Development Co., Ltd., Guangdong provides)
2 methods
Adopt accelerated test to measure the stability of injection use compound red sage root freezing-dried powder injection and FUFANG DANSHEN ZHUSHEYE, the two is placed DL 302 type temperature and humidity regulators, 39 ± 1 ℃, relative humidity under 75% condition respectively at 0,1,2, measure the content of the two Central Plains youngster's aldehyde March.
3 assays
3.1 chromatographic condition and system suitability octadecylsilane chemically bonded silica are filler; Methanol-0.5% acetic acid (20: 80) is mobile phase; Detect wavelength 280nm.
3.2 the selection of detection wavelength is got, and the protocatechualdehyde reference substance solution is an amount of, at 200～400nm wave-length coverage spectra re-recorded curve, protocatechualdehyde has absorption maximum at 280.0nm wavelength place, therefore selects 280nm as detecting wavelength.
3.3 sample preparation is got injection use compound red sage root freezing-dried powder injection of the present invention and is dissolved in water, and measures with external standard method with the FUFANG DANSHEN ZHUSHEYE direct injected.
4 results
Table 1 preliminarily stabilised result of the test table
The protocatechualdehyde content time (moon)
(Mg/ml) March in 0 month 2 month January
The injection use compound Radix Salviae Miltiorrhizae freezes
0.653 0.644 0.650 0.646
The dry powder injection
FUFANG DANSHEN ZHUSHEYE 0.650 0.623 0.610 0.593
Result of the test shows, common FUFANG DANSHEN ZHUSHEYE is under the accelerated test condition, and it is recent 10% that content has descended, and injection use compound red sage root freezing-dried powder injection protocatechualdehyde content of the present invention remains unchanged substantially, has stability preferably.
Test example two: the injection use compound red sage root freezing-dried powder injection is to the influence of Acute Myocardial Ischemia in Rats
1, experimental apparatus and material
Animal: Wistar rat; The pituitrin injection, Beijing biochemical-pharmaceutical factory is produced.
2, method and result
2.1 the compound Salviae Miltiorrhizae ejection preparation is to the influence of rat ischemia ECG T wave due to the pituitrin: get 40 of body weight 250～300g Wistar rats, male and female half and half are divided into 4 groups at random, and 10 every group, ip administration 7d continuously, dosage sees Table 1.Each treated animal is behind last administration 30min, and lumbar injection 25% urethane 0.4ml/100g anaesthetizes, and it is fixing to lie on the back, normal voltage 1mv=15mm, chart drive speed 50mm/s, record II lead electrocardiogram.Sublingual vein injection of pituitrin 0.75u/kg has injected in 5s.Electrocardiogram of every 30s record.In the rat intravenous injection pituitrin 1min, great majority show as decreased heart rate, and the T wave height is alarmmed, and the ST section such as raises at variation.Observe the variation that medication front and back 30s, 1min and 50min go up T ripple propagation respectively.
Table 2 compound Salviae Miltiorrhizae ejection preparation of the present invention and Radix Salviae Miltiorrhizae Injection are to the influence of rat ischemia ECG T wave due to the pituitrin.
T ripple increment (mV)
Group number of animals dosage
30s 1min 5min
Normal saline group 10 0.6ml 0.35 ± 0.12 0.25 ± 0.16 0.18 ± 0.022
Radix Salviae Miltiorrhizae Injection group 10 0.6ml/kg 0.26 ± 0.06* 0.15 ± 0.041* 0.098 ± 0.015*
Compound recipe of the present invention
10 0.6ml/kg 0.19±0.05** 0.10±0.034** 0.052±0.011**
The Radix Salviae Miltiorrhizae Injection group
Verapamil 10 5mg/kg 0.16 ± 0.020** 0.08 ± 0.032** 0.030 ± 0.018**
Compare with the normal saline group: * P＜0.05, * * P＜0.01
Can find out from above result, the T ripple propagation when compound Salviae Miltiorrhizae ejection preparation of the present invention can significantly reduce 30s, 1min and 5min is more obvious than common Radix Salviae Miltiorrhizae Injection effect.
Specific embodiment
Embodiment one
Prescription Radix Salviae Miltiorrhizae 1657.4g Radix Notoginseng 324.2g Borneolum Syntheticum 18.4g
Get salvia piece, decoct with water three times, adding for the first time 8 times of water gagings decocted 2 hours, second and third time adds 6 times of water gagings respectively and decocted 1 hour, merge decoction liquor, filter, subsequent filtrate adsorbs with anion exchange resin, use the sig water eluting after the washing remove impurity, it is 4-5 that the alkali eluent is transferred pH value with acid, and being evaporated to relative density is the extractum of 1.20-1.30 (50 ℃), extractum adds ethanol under condition of stirring makes the alcohol amount of containing reach 60-80%, leave standstill, supernatant reclaims ethanol, and is evaporated to the extractum that relative density is 1.25-1.35 (50 ℃); Extractum adds ethanol while stirring to be made and contains alcohol amount and reach 70-85%, leaves standstill 24 hours, filters, and supernatant reclaims ethanol, and is evaporated to the extractum that relative density is 1.20-1.30 (50 ℃), and vacuum drying gets Radix Salviae Miltiorrhizae extract.
Radix Notoginseng powder is broken into coarse powder, the alcohol reflux three times that adds the 50-80% of 6 times, 5 times, 5 times amounts respectively, 2 hours for the first time, second and third time is 1.5 hours, and merge extractive liquid, filters, after recovery ethanol is extremely most, (extracting solution: medical material=1: 1), high speed centrifugation, supernatant are crossed the D that handles well to thin up
101Macroporous resin adsorption, the washed resin decontamination of 1 times of amount of resin, the ethanol elution of reuse 80% is collected alcohol eluen, reclaims ethanol, and being evaporated to relative density is the extractum of 1.20-1.30 (50 ℃), and vacuum drying gets Radix Notoginseng extract.
Borneolum Syntheticum becomes nearly saturated solution standby with anhydrous alcohol solution; HP-β-CD that other gets 20 times of Borneolum Syntheticum amounts adds the injection water and makes saturated solution, Borneolum Syntheticum ethanol liquid slowly is added drop-wise in HP-β-CD saturated solution, the limit edged stirs, mixing speed per minute 4000 changes, and after Borneolum Syntheticum ethanol liquid adds, continues to stir 5 hours, mixed liquor cold preservation, filter, the precipitation cold drying, standby.
Get Radix Salviae Miltiorrhizae, Radix Notoginseng extract and add injection water 700ml dissolving, boiled cold preservation 15 minutes, filter, the subsequent filtrate molecular cut off is 3000 ultrafilter membrane ultrafiltration, and ultrafiltrate mixes with Borneolum Syntheticum HP-beta-CD inclusion, adds the lyophilizing excipient, adjust volume to 1000ml, transferring pH value is 8.0, and degerming filters, packing, lyophilizing, promptly.
Embodiment two
Prescription Radix Salviae Miltiorrhizae 1657.4g Radix Notoginseng 324.2g Borneolum Syntheticum 18.4g
Get salvia piece, decoct with water three times, adding for the first time 8 times of water gagings decocted 2 hours, second and third time adds 6 times of water gagings respectively and decocted 1 hour, merge decoction liquor, filter, subsequent filtrate adsorbs with anion exchange resin, use the sig water eluting after the washing remove impurity, it is 4-5 that the alkali eluent is transferred pH value with acid, and being evaporated to relative density is the extractum of 1.20-1.30 (50 ℃), extractum adds ethanol under condition of stirring makes the alcohol amount of containing reach 60-80%, leave standstill, supernatant reclaims ethanol, and is evaporated to the extractum that relative density is 1.25-1.35 (50 ℃); Extractum adds ethanol while stirring to be made and contains alcohol amount and reach 70-85%, leaves standstill 24 hours, filters, and supernatant reclaims ethanol, and is evaporated to the extractum that relative density is 1.20-1.30 (50 ℃), and vacuum drying gets Radix Salviae Miltiorrhizae extract.
Radix Notoginseng powder is broken into coarse powder, the alcohol reflux three times that adds the 50-80% of 6 times, 5 times, 5 times amounts respectively, 2 hours for the first time, second and third time is 1.5 hours, merge extractive liquid,, filter, after recovery ethanol is extremely most, thin up (extracting solution: medical material=1: 1), high speed centrifugation, supernatant is crossed the AB-8 type macroporous resin adsorption of handling well, first washing decontamination with 1 times of amount of resin, the ethanol elution of reuse 70%, collect alcohol eluen, reclaim ethanol, being evaporated to relative density is the extractum of 1.20-1.30 (50 ℃), and vacuum drying gets Radix Notoginseng extract.
Borneolum Syntheticum becomes nearly saturated solution standby with anhydrous alcohol solution; HP-β-CD that other gets 20 times of Borneolum Syntheticum amounts adds the injection water and makes saturated solution, Borneolum Syntheticum ethanol liquid slowly is added drop-wise in HP-β-CD saturated solution, the limit edged stirs, mixing speed per minute 4000 changes, and after Borneolum Syntheticum ethanol liquid adds, continues to stir 5 hours, mixed liquor cold preservation, filter, the precipitation cold drying, standby.
Get Radix Salviae Miltiorrhizae, Radix Notoginseng extract and add injection water 700ml dissolving, boiled cold preservation 15 minutes, filter, the subsequent filtrate molecular cut off is 3000 hollow fiber column ultrafilter, and ultrafiltrate mixes with Borneolum Syntheticum HP-beta-CD inclusion, adds the lyophilizing excipient, adjust volume to 1000ml, transferring pH value is 8.0, and degerming filters, packing, lyophilizing, promptly.
Claims (5)
1, a kind of injection use compound red sage root freezing-dried powder injection, its raw material is Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum, it is characterized in that: it is made up of the water solubility extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum hydroxypropyl clathrate and water solublity pharmaceutic adjuvant, promptly makes by following preparation method:
(1) gets the red rooted salvia decoction pieces, decoct with water three times, merge decoction liquor, filter, subsequent filtrate adsorbs with anion exchange resin, wash reuse sig water eluting behind the decontamination earlier with water, the alkali eluent is 4-5 with sour adjust pH, and relative density is the extractum of 1.20-1.30 when being evaporated to 50 ℃, adding ethanol makes the alcohol amount of containing reach 60-80%, leave standstill, supernatant reclaims ethanol, and relative density is the extractum of 1.25-1.35 when being evaporated to 50 ℃; Extractum adds ethanol while stirring to be made and contains alcohol amount and reach 70-85%, leaves standstill 24 hours, filters, and supernatant reclaims ethanol, and relative density is the extractum of 1.20-1.30 when being evaporated to 50 ℃, and vacuum drying gets Radix Salviae Miltiorrhizae extract;
(2) Radix Notoginseng powder is broken into coarse powder, with the alcohol reflux of 50-80% three times, and merge extractive liquid,, filter, after recovery ethanol is extremely most, thin up, high speed centrifugation, supernatant is crossed the macroporous adsorptive resins of having handled well, first washing decontamination with 1 times of resin column volume, the ethanol elution of reuse 50-80%, collect alcohol eluen, reclaim ethanol, relative density is the extractum of 1.20-1.30 when being evaporated to 50 ℃, and vacuum drying gets Radix Notoginseng extract;
(3) Borneolum Syntheticum becomes nearly saturated solution standby with anhydrous alcohol solution; Other gets HP-β-CD and adds the injection water and make saturated solution, and Borneolum Syntheticum ethanol liquid slowly is added drop-wise in HP-β-CD saturated solution, and the limit edged stirs, after Borneolum Syntheticum ethanol liquid adds, continue stirred for several hour, mixed liquor cold preservation, filter, the precipitation cold drying gets Borneolum Syntheticum HP-beta-CD inclusion;
(4) get above-mentioned Radix Salviae Miltiorrhizae, Radix Notoginseng extract and add the dissolving of injection water, filter, filtrate is 3000 ultrafilter membrane ultrafiltration with molecular cut off, ultrafiltrate mixes with Borneolum Syntheticum HP-beta-CD inclusion, adds freeze-dried excipient, and adjust pH is 5.0-6.5,80 ℃ of insulations of active carbon with 0.2% 15 minutes, filter, add the injection water, regulate pH value to 8.0 to ormal weight, filter, cool-drying is frozen in fill, promptly.
2, the preparation method of the described compound red sage root freezing-dried powder injection of claim 1 is characterized in that it comprises following preparation process:
Get salvia piece, decoct with water three times, adding for the first time 8 times of water gagings decocted 2 hours, second and third time adds 6 times of water gagings respectively and decocted 1 hour, merge decoction liquor, filter, subsequent filtrate adsorbs with anion exchange resin, use the sig water eluting after the washing remove impurity, it is 4-5 that the alkali eluent is transferred pH value with acid, and relative density is the extractum of 1.20-1.30 when being evaporated to 50 ℃, extractum adds ethanol under condition of stirring makes the alcohol amount of containing reach 60-80%, leave standstill, supernatant reclaims ethanol, and relative density is the extractum of 1.25-1.35 when being evaporated to 50 ℃; Extractum adds ethanol while stirring to be made and contains alcohol amount and reach 70-85%, leaves standstill 24 hours, filters, and supernatant reclaims ethanol, and relative density is the extractum of 1.20-1.30 when being evaporated to 50 ℃, and vacuum drying gets Radix Salviae Miltiorrhizae extract;
Radix Notoginseng powder is broken into coarse powder, the alcohol reflux three times that adds the 50-80% of 6 times, 5 times, 5 times amounts respectively, 2 hours for the first time, second and third time was 1.5 hours, merge extractive liquid,, extracting solution: medical material=1: 1, filter, after recovery ethanol is extremely most, thin up, high speed centrifugation, supernatant are crossed the D that handles well
101Macroporous resin adsorption, the washed resin decontamination of 1 times of amount of resin, the ethanol elution of reuse 80% is collected alcohol eluen, reclaims ethanol, and relative density is the extractum of 1.20-1.30 when being evaporated to 50 ℃, and vacuum drying gets Radix Notoginseng extract;
Become nearly saturated solution standby with anhydrous alcohol solution Borneolum Syntheticum; HP-β-CD that other gets 20 times of Borneolum Syntheticum amounts adds the injection water and makes saturated solution, Borneolum Syntheticum ethanol liquid slowly is added drop-wise in HP-β-CD saturated solution, the limit edged stirs, mixing speed per minute 4000 changes, and after Borneolum Syntheticum ethanol liquid adds, continues to stir 5 hours, mixed liquor cold preservation, filter, the precipitation cold drying, standby; Get Radix Salviae Miltiorrhizae, Radix Notoginseng extract and add injection water 700ml dissolving, boiled 15 minutes, cold preservation filters, the subsequent filtrate molecular cut off is 3000 ultrafilter membrane ultrafiltration, ultrafiltrate mixes with Borneolum Syntheticum HP-beta-CD inclusion, adds freeze-dried excipient, adjusts volume to 1000ml, transferring pH value is 8.0, degerming filters, packing, lyophilizing.
3, compound red sage root freezing-dried powder injection according to claim 1 is characterized in that: adsorbent resin wherein can be the macroporous resin of nonpolar or low pole.
4, compound red sage root freezing-dried powder injection according to claim 3 is characterized in that: adsorbent resin wherein is D
101With AB-8 type macroporous resin.
5, compound red sage root freezing-dried powder injection according to claim 1 is characterized in that: freeze-dried excipient wherein is the mixture of a kind of in mannitol and the lactose or two kinds.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1297278C (en) * | 2004-07-28 | 2007-01-31 | 广东天之骄生命科技有限公司 | Medicinal composition containing salvianolic acid B, total ara-saponin and camphol and its preparation and use |
| CN1297279C (en) * | 2004-07-28 | 2007-01-31 | 广东天之骄生命科技有限公司 | Medicinal composition containing danshensu, total ara-saponin and camphol and its preparation and use |
| CN101084998B (en) * | 2006-06-08 | 2011-10-26 | 天津天士力之骄药业有限公司 | Compound red sage root freezing-dried powder injection |
| CN101084997B (en) * | 2006-06-08 | 2012-06-06 | 天津天士力之骄药业有限公司 | Traditional Chinese medicine freezing-dried powder injection for treating cardiovascular and cerebrovascular diseases and its preparing method |
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| CN1144673A (en) * | 1995-09-04 | 1997-03-12 | 张相国 | Red sage root and its composite compound red sage root powder injection and preparation method |
| CN1202103C (en) * | 2002-05-23 | 2005-05-18 | 天津天士力制药股份有限公司 | Preparation method of red sageroot total phenolic acid and its use |
| CN1422653A (en) * | 2002-11-09 | 2003-06-11 | 边冬梅 | Effective part of root of red-rooted salvia and compound powder injecta of root of red-rooted salvia and preparation method and use of said medicine |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1297278C (en) * | 2004-07-28 | 2007-01-31 | 广东天之骄生命科技有限公司 | Medicinal composition containing salvianolic acid B, total ara-saponin and camphol and its preparation and use |
| CN1297279C (en) * | 2004-07-28 | 2007-01-31 | 广东天之骄生命科技有限公司 | Medicinal composition containing danshensu, total ara-saponin and camphol and its preparation and use |
| CN101084998B (en) * | 2006-06-08 | 2011-10-26 | 天津天士力之骄药业有限公司 | Compound red sage root freezing-dried powder injection |
| CN101084997B (en) * | 2006-06-08 | 2012-06-06 | 天津天士力之骄药业有限公司 | Traditional Chinese medicine freezing-dried powder injection for treating cardiovascular and cerebrovascular diseases and its preparing method |
| CN102688426A (en) * | 2012-06-25 | 2012-09-26 | 许梅 | Traditional Chinese medicine composition for treating acute upper gastrointestinal hemorrhage, as well as preparation method and application thereof |
| CN102688426B (en) * | 2012-06-25 | 2013-12-18 | 青岛华仁技术孵化器有限公司 | Traditional Chinese medicine composition for treating acute upper gastrointestinal hemorrhage, as well as preparation method and application thereof |
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