CN1225276C - Red peony root injection and its preparation method - Google Patents
Red peony root injection and its preparation method Download PDFInfo
- Publication number
- CN1225276C CN1225276C CN 03139942 CN03139942A CN1225276C CN 1225276 C CN1225276 C CN 1225276C CN 03139942 CN03139942 CN 03139942 CN 03139942 A CN03139942 A CN 03139942A CN 1225276 C CN1225276 C CN 1225276C
- Authority
- CN
- China
- Prior art keywords
- injection
- present
- preparation
- radix paeoniae
- paeoniae rubra
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention discloses a red peony root injection which is prepared from traditional Chinese medicine red peony root as a raw material through alcohol extraction, n-butanol extraction or macroporous resin column chromatography purification, and a right amount of pharmaceutic adjuvants and water for injection is added. The present invention comprises a small content injection and large content transfusion. The present invention has high stability and long effective period, and can be used for intramuscular injection, intravenous injection or intravenous drip. Pharmacodynamic experiments show that the present invention can obviously improve the behavior disorder of a rat with cerebral infarction, reduce the area of cerebellar infarction, obviously reduce the water content of infracted brain tissue, relieve the lipoid peroxidation damage of the brain tissue and increase the capacity of the rat for resisting acute hypoxia; the present invention has favorable therapeutic effects on the cerebral infarction.
Description
Technical field
The present invention relates to a kind of preparation method of Radix Paeoniae Rubra injection.
Background technology
Radix Paeoniae Rubra is traditional conventional Chinese medicine, derives from the dry root of ranunculaceae plant Radix Paeoniae Paeonia Lactiflora Pall. or river Radix Paeoniae Rubra Paeonia veilchii Lyncn.Record in one one of Pharmacopoeia of the People's Republic of China version in 2000, have the effect of clearing away heat and cooling blood, eliminating stasis to stop pain, clinically be used for diseases such as maculae caused by violent heat pathogen, hematemesis and epistaxis, conjunctival congestion and swelling pain, hypochondriac pain due to stagnation of liverQI, amenorrhea are stimulated the menstrual flow, injury from falling down.Pharmacological research in recent years shows that Radix Paeoniae Rubra has many-sided pharmacological actions such as protection heart, coronary blood flow increasing, antithrombotic formation and atherosclerosis, sedation and analgesia, anti-inflammatory, antibacterial, antioxidation.Fitochemical studies result shows that the main effective ingredient of Radix Paeoniae Rubra is monoterpenes chemical compounds such as peoniflorin, lactone glucoside of Radix Paeoniae, Hydroxy peoniflorin.The Radix Paeoniae Rubra injection that uses clinically at present is the little liquid drugs injection of water alcohol method preparation, and active constituent content is low, and quality is stable inadequately, has influenced therapeutic effect.Press at present active constituent content height, steady quality, effect duration is long, curative effect is high Radix Paeoniae Rubra injection clinically.
Summary of the invention
The object of the present invention is to provide the preparation method of the long Radix Paeoniae Rubra injection of a kind of active constituent content height, curative effect height, steady quality, effect duration, the preparation method that comprises little liquid drugs injection and infusion solutions, this injection can be used for intramuscular injection, intravenous injection or intravenous drip.
The preparation method of a kind of Radix Paeoniae Rubra injection provided by the invention, this method comprise following three steps:
(1) extracts: get the Radix Paeoniae Rubra medical material, section is measured 60～80% alcohol reflux 2～4 times, each 0.5～3 hour with 4～12 times at every turn, merge extractive liquid,, filter, decompression filtrate recycling ethanol and to be concentrated into relative density be 1.15～1.25 concentrated solution adds the water of 2～5 times of amounts, stir, cold preservation 12～72 hours, high speed centrifugation, supernatant are evaporated to the clear paste of relative density 1.25～1.30, adding ethanol makes and contains alcohol amount to 80～85%, stir evenly, cold preservation 12～48 hours, the leaching supernatant adds ammonia and transfers pH to 8.0, cold preservation 12～48 hours, filter, decompression filtrate recycling ethanol and to be concentrated into relative density be 1.05～1.18 concentrated solution, extracting solution;
(2) purification: get said extracted liquid, adopt n-butanol extraction or macroporous resin column chromatography legal system to get the purification thing;
(3) preparation: get above-mentioned purification thing, add the dissolving of injection water, transfer pH to 5.0～5.5, heated and boiled 5～10 minutes, cold preservation filters, and filtrate is used the ultrafilter membrane ultrafiltration of molecular cut off 3000, get filtrate and add injection water and injection pharmaceutic adjuvant, stirring and dissolving is transferred pH to 6.0～7.0, with the microporous filter membrane filtration of 0.22 μ m, filtrate embedding, sterilization, quality inspection make injection.
N-butanol extraction described in the above-mentioned preparation method step (2) is: gets extracting solution, uses isopyknic n-butanol extraction at every turn, and coextraction 3～6 times, combining extraction liquid, reclaim under reduced pressure, drying promptly get the purification thing; Described macroporous resin column chromatography method is: get extracting solution, be added on the macroporous adsorption resin chromatography post, use the water elution of 10～50 times of extracting solution weight earlier, discard eluent, 10～30% ethanol elutions that reuse extracting solution weight is 10～50 times, collect this eluent, reclaim under reduced pressure, concentrated, dry promptly gets the purification thing; The described injection pharmaceutic adjuvant of step (3) is one or more in mannitol, sodium chloride, sorbitol, glucose, fructose, the sodium sulfite.
The Radix Paeoniae Rubra injection of the inventive method preparation has good stability, studies show that through stability test to be valid up to 2.1 years, substantially exceeds the effect duration in 1.5 years of present Radix Paeoniae Rubra injection; Indexs such as clarity, color and luster, pH value, thermal source, zest all meet " the regulation of the relevant injection of Chinese pharmacopoeia; Can be used for intramuscular injection, intravenous drip or intravenous administration.The injection of the inventive method preparation has easy to use, advantages such as onset is rapid, bioavailability is high, definite effect, show through pharmacodynamics test: this injection can obviously improve the behavior disorder of cerebral infarction rat, reduce cerebral infarct size, significantly reduce the infraction brain water content, alleviate the lipid peroxidation injury of cerebral tissue, improve the ability of the anti-acute anoxia of mouse brain, cerebral infarction is had the good curing effect.
The specific embodiment
Embodiment 1
Get Radix Paeoniae Rubra medical material 400g, be cut into decoction pieces, measure 70% alcohol reflux 2 times with 6 times, 2 hours for the first time, 1 hour for the second time, merge extractive liquid,, filter, decompression filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.18 (50 ℃), and the water that adds 4 times of amounts stirs evenly, cold preservation 24 hours, high speed centrifugation (20000r/min), supernatant is evaporated to the clear paste of relative density 1.25 (50 ℃), add ethanol and make and contain alcohol amount to 85%, cold preservation 24 hours, the leaching supernatant adds ammonia and transfers pH to 8.0, cold preservation 24 hours, filter, decompression filtrate recycling ethanol also is concentrated into the concentrated solution that relative density is 1.08 (50 ℃), uses the water saturated n-butanol extraction of equal-volume 4 times at every turn, combining extraction liquid, the reclaim under reduced pressure n-butyl alcohol also is concentrated into the thick paste that relative density is 1.25 (50 ℃), and vacuum drying gets Radix Paeoniae Rubra extract.Get Radix Paeoniae Rubra extract, add injection water 600ml dissolving, transfer pH to 5.0～5.5 with 40% sodium hydroxide solution, heated and boiled 5 minutes, put cold, cold preservation 24 hours, filter, filtrate is got filtrate and is added the injection water to 1000ml with the ultrafilter membrane ultrafiltration of molecular cut off 3000, add 0.05% sodium sulfite and 0.8% sodium chloride again, transfer pH to 6.0～7.0 with 40% sodium hydroxide solution, with the microporous filter membrane filtration of 0.22um, the filtrate embedding is in the infusion bottle of 100ml, sterilization, quality inspection promptly make injection of the present invention---infusion solutions.
Embodiment 2
Get Radix Paeoniae Rubra medical material 300g, be cut into decoction pieces, with 8 times of amount 60% alcohol reflux 3 times, each 1.5 hours, merge extractive liquid,, filter, decompression filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.23 (50 ℃), and the water that adds 3 times of amounts stirs evenly, cold preservation 36 hours, high speed centrifugation (20000r/min), supernatant is evaporated to the clear paste of relative density 1.27 (50 ℃), add ethanol and make and contain alcohol amount to 80%, cold preservation 48 hours, the leaching supernatant adds ammonia and transfers pH to 8.0, cold preservation 28 hours, filter, decompression filtrate recycling ethanol also is concentrated into the concentrated solution that relative density is 1.14 (50 ℃), is added on the macroporous adsorption resin chromatography post, use the water elution of 30 times of concentrated solution weight earlier, discard eluent, 20% ethanol elution that reuse concentrated solution weight is 30 times is collected this eluent, reclaim under reduced pressure, concentrate, drying promptly gets the purification thing.Get this purification thing, add injection water 800ml dissolving, transfer pH to 5.0～5.5 with 40% sodium hydroxide solution, heated and boiled 6 minutes, put cold, cold preservation 24 hours, filter, filtrate is got filtrate and is added the injection water to 1000ml with the ultrafilter membrane ultrafiltration of molecular cut off 3000, the mannitol that adds 0.04% sodium sulfite, 0.2% sodium chloride 4.8% again, transfer pH to 6.0～7.0 with 40% sodium hydroxide solution, with the microporous filter membrane filtration of 0.22um, the filtrate embedding is in the infusion bottle of 250ml, sterilization, quality inspection promptly make injection of the present invention---infusion solutions.
Embodiment 3
Get Radix Paeoniae Rubra medical material 1000g, be cut into decoction pieces, measure 70% alcohol reflux 3 times with 8 times, each 1 hour, merge extractive liquid, filters, and decompression filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.16 (50 ℃), the water that adds 5 times of amounts stirs evenly, cold preservation 36 hours, high speed centrifugation (20000r/min), supernatant are evaporated to the clear paste of relative density 1.26 (50 ℃), add ethanol and make and contain alcohol amount to 85%, cold preservation 24 hours, the leaching supernatant adds ammonia and transfers pH to 8.0, and cold preservation 30 hours filters, decompression filtrate recycling ethanol also is concentrated into the concentrated solution that relative density is 1.10 (50 ℃), use the water saturated n-butanol extraction of equal-volume 5 times at every turn, combining extraction liquid, the reclaim under reduced pressure n-butyl alcohol also is concentrated into the thick paste that relative density is 1.25 (50 ℃), vacuum drying gets Radix Paeoniae Rubra extract.Get Radix Paeoniae Rubra extract, add injection water 800ml dissolving, transfer pH to 5.0～5.5 with 40% sodium hydroxide solution, heated and boiled 5 minutes, put cold, cold preservation 24 hours, filter, filtrate is got filtrate and is added the injection water to 1000ml with the ultrafilter membrane ultrafiltration of molecular cut off 3000, add 0.05% sodium sulfite and 0.2% sodium chloride again, transfer pH to 6.0～7.0 with 40% sodium hydroxide solution, with the microporous filter membrane filtration of 0.22um, the filtrate embedding is in the ampoule of 2～10ml, sterilization, quality inspection promptly make injection of the present invention---little liquid drugs injection.
Pharmacodynamic test of active extract
The therapeutical effect of 1 pair of intraluminal middle cerebral artery occlusion in rats bolt collimation method focal cerebral ischemia model (MACO)
1.1 experimental technique
Modeling method: the 280-300g male SD rat is anaesthetized neck median incision, separation, ligation right carotid, external carotid artery and bifurcated artery thereof with 10% chloral hydrate 3ml/kg lumbar injection (ip).Separate the right side internal carotid artery, separate wing jaw tremulous pulse downwards along internal carotid artery, this branch of root ligation.Be equipped with line, far-end placement bulldog clamp at the internal carotid artery near-end, common carotid artery crotch otch inserts the 4-0 nylon wire, and its degree of depth is 17～20mm, and the bolt line enters internal carotid artery, goes into cranium to anterior cerebral artery, all blood flows sources of blocking-up middle cerebral artery.Remove bulldog clamp, tighten line fully, stay the long the end of a thread of 1cm outward, skin suture.1 hour posterior vein of ischemia is injected (iv) administration or iv normal saline.Skin need not anaesthetized and cut to perfusion more once more behind the ischemia 2h, lift gently institute's the end of a thread that stays to resistance is arranged time prompting nylon wire head end to the common carotid artery incision, blood flow is logical again.Sham operated rats is except that plug wire not, and all the other steps are the same.
Experiment grouping and administration: (1) sham operated rats; (2) model (solvent treatment) group; (3) injection iv small dose group of the present invention; (4) the heavy dose of group of dosage group (5) injection iv of the present invention among the injection iv of the present invention; (6) Radix Salviae Miltiorrhizae Injection iv treatment group.
30min and 12h are respectively by each dosed administration once after modeling.
Observation index:
(1) neurological's scoring
After the survival Mus is poured into 24h again, observe rat behavior and learn variation, carry out neurological's scoring.
5 fens system standards of grading with reference to Zea Longa:
0 minute, impassivity damage symptom;
1 minute, can not full extension offside fore paw;
2 minutes, turn-take laterally;
3 minutes, topple over to offside;
4 minutes, can not spontaneously walk loss of consciousness.
(2) mensuration of cerebral infarction scope: carry out behind above-mentioned two index determinings the rat broken end and get brain, be cut into 5 after removing olfactory bulb, cerebellum and low brain stem, dye with red tetrazolium (TTC).Take on a red color after normal structure is dyed, blocking tissue is white in color.Calculate blocking tissue's weight and account for the heavy percentage ratio of total brain as infarction size.
(3) brain water content is measured: after neurological's scoring, broken end is got the Mus brain fast.A part is divided another name left and right sides brain hemisphere weight in wet base, puts 100 ℃ of baking boxs and dries to constant weight, calculates brain water content as follows, brain water content (%)=(weight in wet base-dry weight)/weight in wet base * 100%.
(4) mensuration of cerebral tissue biochemical indicator: the part animal is got cerebral tissue carry out SOD, LPO content in the homogenate mensuration cerebral tissue.
(5) pathologic finding: fixing in another part 10% formalin, prepare tissue slice through steps such as dehydration, embedding, section, dyeing, carry out histopathologic examination.
1.2 result
1.2.1 overview
Promptly there is hemiplegia sample symptom to occur after the rat anesthesia of process cerebral infarction is clear-headed.Mainly show as in various degree the operation offside forelimb and receive, the shoulder inward turning, muscular tension reduces, and pushes away right shoulder to side shifting, and resistance reduces, even some animal also occurs ceaselessly to the side phenomenon of turn-taking.Table 1 shows, compares with model group (normal saline treatment), and each dosage treatment group of behavior scoring the present invention of postoperative 24h and Treated with Radix Salviae Miltiorrhizae group all have obviously low behavioristics's scoring, and there were significant differences for statistical analysis (P＜0.01).The general state of postoperative model group animal is relatively poor, the movable minimizing, and most of the weight of animals descend to some extent, all improve significantly and respectively treat the general situation of treated animal.
Choose preceding 8 rats of each experimental group and carry out neurological scoring, iv injection height of the present invention, middle group of rat and model group comparison, the behavior disorder of rat improves (P＜0.01) significantly, and it is normal that some animal almost completely recovers.Sham operated rats animal behavior no abnormal (seeing Table 1).
Table 1 injection of the present invention is to the influence (x ± s) that marks of the neurological after the intraluminal middle cerebral artery occlusion in rats infraction
| Group | Dosage (g/kg) | n | Neurological's scoring |
| Sham-operation | - | 10 | 0 |
| Model | - | 9 | 1.6±0.77 |
| Radix Salviae Miltiorrhizae | 10ml/kg | 8 | 0.8±0.75 * |
| The present invention | 8 | 8 | 0.5±0.32** |
| 4 | 9 | 0.6±0.57** | |
| 2 | 9 | 0.9±0.83 * |
Compare with model group
*P＜0.05,
*P＜0.01,
* *P＜0.001
1.2.2 the observation of rat cerebral infarction scope and injection of the present invention are to the influence of infarction size
As can be seen from Table 2, cerebral tissue infraction degree is obvious behind the cerebral ischemia re-pouring 24h, and infarct size accounts for 36.68 ± 10.51% of total brain area.After injection of the present invention and the Radix Salviae Miltiorrhizae Injection administration, cerebral infarct size percentage ratio is obviously descended.The sham operated rats animal does not see that cerebral infarction takes place.
Table 2 injection of the present invention is to the protective effect of focal brain ischemia-reperfusion injury in rats (x ± s)
| Group | n | Dosage (g/kg) | Infarct size (%) |
| Model group | 9 | 0 | 36.68±10.51 |
| The Radix Salviae Miltiorrhizae group | 8 | 10ml/kg | 13.32±4.77 *** |
| The present invention | 8 | 2 | 19.96±7.28 ** |
| The present invention | 8 | 4 | 12.13±7.45 *** |
| The present invention | 9 | 8 | 8.05±2.51 *** |
Compare with model group,
*P＜0.01,
* *P＜0.001.
1.2.3 brain water content
As can be seen from Table 3, each organizes the weight in wet base of the left side brain that rat do not block, and dry weight does not all have tangible difference; And for the right side cerebral tissue that blocks, the model group brain water content is significantly higher than sham operated rats; Heavy dose of group of injection of the present invention and middle dosage group then significantly are lower than model control group, and it is approaching with sham operated rats, though the brain water content of injection small dose group of the present invention has reduction trend, but compare not statistically significant with model control group, Radix Salviae Miltiorrhizae Injection treatment group also has the effect that reduces brain water content.
The comparison of table 3 cerebral infarction rat brain water content (x ± s, n=8)
| Group dosage (g/kg) | Left side brain | Right brain | ||||
| Weight in wet base (mg) | Dry weight (mg) | Water content (%) | Weight in wet base (mg) | Dry weight (mg) | Water content (%) | |
| Sham-operation | 784.6±34.2 | 180.1±10.9 | 77.0±0.93 | 793.1±55.2 | 182.8±17.9 | 77.0±0.93 |
| Model group | 813.1±20.6 | 187.1±11.8 | 77.0±1.32 | 838.1±64.2 | 171.6±12.1 | 79.5±0.73** |
| Radix Salviae Miltiorrhizae 10ml/kg | 813.6±41.5 | 186.9±14.8 | 77.0±1.01 | 862.6±29.6 | 181.8±10.3 | 78.3±1.37# |
| The present invention 2 | 814.9±39.9 | 188.1±18.1 | 76.9±1.43 | 847.1±42.8 | 179.0±5.51 | 78.7±0.29 |
| The present invention 4 | 826.0±37.9 | 189.8±10.7 | 77.0±1.14 | 833.0±53.7 | 179.5±11.9 | 78.4±1.05# |
| The present invention 8 | 835.1±38.8 | 190.8±18.9 | 77.2±1.35 | 865.8±45.9 | 193.0±15.0 | 77.7±0.88## |
Compare with sham operated rats,
*P＜0.01; Compare with model group:
#P＜0.05,
##P＜0.01.
1.2.4 the variation of cerebral tissue superoxide dismutase, lipid peroxide level
24h observes after the modeling, and the LPO of model group rat cerebral tissue content all significantly increases than normal group, and SOD content significantly reduces.Big or middle dosage group of Radix Salviae Miltiorrhizae group and injection of the present invention and model group compare, and LPO content all reduces; Injection group SOD content of the present invention all increases.Point out the injection of the present invention tissue SOD's content that can raise, reduce the LPO level, thereby alleviate the lipid peroxidation injury of cerebral tissue.See Table 4.
Table 4 injection of the present invention is to the influence of rat cerebral even slurry SOD, LPO content (x ± s)
| Group | LPO(nmol/100mg.Pro) | SOD(U/mg.Pro) |
| The normal control group | 256.11±88.21 | 17.36±2.31* |
| Model group | 378.88±105.78 | 13.12±3.98 |
| The Radix Salviae Miltiorrhizae group | 292.23±85.87* | 20.61±3.83** |
| The heavy dose of group of the present invention | 249.11±96.28** | 25.43±4.25** |
| Dosage group among the present invention | 293.09±48.39** | 20.31±3.61** |
| Small dose group of the present invention | 311.26±144.39 | 19.25±3.57* |
1.2.5 the influence of tectology variation and injection of the present invention behind the rat cerebral infarction
Rat is through cerebral infarction postoperative 24h, and focus side brain surface is pale, unglazed, and the brain vascular surface is than offside hyperemia, and number of blood vessel also increases to some extent, one section middle cerebral artery colour-darkening between tractus olfactorius and inferior cerebral vein.Postoperative 48h focus side cerebral tissue edema is obvious, and prolongation in time engenders softening.Observe brain tissue slice under light microscopic, in the visible middle cerebral artery thrombosis is arranged, the thrombosis composition mainly is platelet, erythrocyte and fibrin, shows as the feature of mixed thrombus.Cerebral tissue mainly is ischemic change, prolongs in time, and the softening kitchen range scope of ischemia and the degree of depth increase to some extent.Sham operated rats does not have obvious pathological change.
Animal after the present invention's treatment, naked eyes are that visible middle cerebral artery is ruddy than control animals, tissue slice shows that thrombosis obviously alleviates even dissolving fully.The cerebral tissue degree of ischemia alleviates, and has only small pieces to soften kitchen range.And the animal of Radix Salviae Miltiorrhizae group, thrombosis also obviously alleviates.Each experimental group cerebral tissue pathological change is as follows:
Sham operated rats: neuron and brain parenchymal cell structure are normal substantially, and nucleus is not seen swelling, and kernel is clear, and tiger spot is high-visible, and the cell peripheral gap slightly enlarges, and slight hyperemia is arranged in the blood capillary, are slight degeneration edema and change.
Model (normal saline treatment) group: left side cerebral hemisphere structure is normal substantially, is Mild edema and changes; The right side sees that neuron and brain parenchymal cell peripheral clearance obviously enlarge, and nucleus swelling is obvious, and kernel is fuzzy, has hemorrhagely in the brain essence, and blood capillary peripheral clearance enlarges, and becomes degeneration, necrosis, hemorrhage change.
The Radix Salviae Miltiorrhizae Injection group: left side brain cell structure no abnormality seen, rarely seen cell peripheral gap slightly increases, and is slight distortion, the edema performance.Right side neuron and nucleus mild swelling, kernel is unclear, and brain parenchymal cell peripheral clearance increases, and around the blood capillary a small amount of exudative hemorrhage is arranged, and is degeneration, edema and hemorrhage change.
The big dose of amount of being group of injection of the present invention: left side brain cell structure no abnormality seen, the slightly broadening of cell peripheral gap is slight distortion and changes.Right side neuron and brain parenchymal cell, blood capillary peripheral clearance slightly increase, neuronal cell nuclear mild swelling, and kernel is clear, visible more kytoplasm hyperplasia phenomenon.Be degeneration, edema changes.
The agent amount of being group in the injection of the present invention: left side brain cell structure no abnormality seen, the cell peripheral gap slightly increases, and is slight distortion and changes.Right side neuron and brain parenchymal cell, blood capillary peripheral clearance slightly increase, neuronal cell nuclear mild swelling, and kernel loses, and visible more glial cells hyperplasia is degeneration, and edema changes.
Injection small dose group of the present invention: left side brain cell structure no abnormality seen, the cell peripheral gap slightly increases.Neuron and brain parenchymal cell, blood capillary peripheral clearance slightly increase, the cell Mild edema, and kernel is unclear, and hyperemia is arranged in the blood capillary, and peripheral clearance increases, and is degeneration, and edema changes.
2. to the influence of chmice acute cerebral hemorrhage
50 of Kunming mouses, body weight 18-22g is divided into 5 groups at random, and 10 every group, medication group iv respectively gives injection 4g/kg of the present invention, 8g/kg, 16g/kg; Positive controls Radix Salviae Miltiorrhizae Injection 20ml/kg, 5% glucose injection of capacity such as normal saline group iv.Successive administration 3d, after the last administration 30min with mice by broken end only, immediately by breathe to dehiscing behind the stopwatch record mice broken end dwell time, dehisce number of times and clotting time.The results are shown in Table 5.
The result shows, all can obviously prolong mice broken end dehisce number of times and breathing time after each dosage group administration of injection of the present invention, and clotting time also prolongs, and is the most remarkable with low dose group of the present invention.Show that the present invention can improve the ability of the anti-acute anoxia of mouse brain, improve brain energy metabolism, and have the effect of blood circulation promoting and blood stasis dispelling.
Table 5 injection of the present invention is to the influence (n=10) of chmice acute cerebral ischemia and clotting time
| Group | Dosage (g/kg) | The number of times of dehiscing | Mouth breathing continuous time (s) | Clotting time (s) |
| 5% glucose injection | - | 11.8±2.0 | 14.2±2.3 | 49.6±16.5 |
| Low dose group of the present invention | 4 | 16.1±3.3** | 17.9±2.7** | 86.1±61.2** |
| Dosage group among the present invention | 8 | 13.9±2.6 * | 19.1±2.2** | 75.1±19.1* |
| High dose group of the present invention | 16 | 14.8±3.4 * | 19.2±1.8** | 76.2±16.3* |
| The Radix Salviae Miltiorrhizae group | 20ml/kg | 14.8±3.4 * | 19.7±3.0** | 60.1±21.2* |
Compare with 5% glucose injection group,
*P＜0.05,
*P＜0.01
Above experimental result shows, the present invention has good therapeutical effect to cerebral infarction.
Claims (4)
1, a kind of preparation method of Radix Paeoniae Rubra injection, this method comprise following three steps:
(1) extracts: get the Radix Paeoniae Rubra medical material, section is measured 60～80% alcohol reflux 2～4 times, each 0.5～3 hour with 4～12 times at every turn, merge extractive liquid,, filter, decompression filtrate recycling ethanol and to be concentrated into relative density be 1.15～1.25 concentrated solution adds the water of 2～5 times of amounts, stir, cold preservation 12～72 hours, high speed centrifugation, supernatant are evaporated to the clear paste of relative density 1.25～1.30, adding ethanol makes and contains alcohol amount to 80～85%, stir evenly, cold preservation 12～48 hours, the leaching supernatant adds ammonia and transfers pH to 8.0, cold preservation 12～48 hours, filter, decompression filtrate recycling ethanol and to be concentrated into relative density be 1.05～1.18 concentrated solution, extracting solution;
(2) purification: get said extracted liquid, adopt n-butanol extraction or macroporous resin column chromatography legal system to get the purification thing;
(3) preparation: get above-mentioned purification thing, add the dissolving of injection water, transfer pH to 5.0～5.5, heated and boiled 5～10 minutes, cold preservation filters, and filtrate is used the ultrafilter membrane ultrafiltration of molecular cut off 3000, get filtrate and add injection water and injection pharmaceutic adjuvant, stirring and dissolving is transferred pH to 6.0～7.0, with the microporous filter membrane filtration of 0.22 μ m, filtrate embedding, sterilization, quality inspection make injection.
2, the preparation method of Radix Paeoniae Rubra injection according to claim 1 is characterized in that the described n-butanol extraction of step (2) is: get extracting solution, use isopyknic n-butanol extraction at every turn, coextraction 3～6 times, combining extraction liquid, reclaim under reduced pressure, drying promptly get the purification thing.
3, the preparation method of Radix Paeoniae Rubra injection according to claim 1, it is characterized in that the described macroporous resin column chromatography method of step (2) is: get extracting solution, be added on the macroporous adsorption resin chromatography post, use the water elution of 10～50 times of extracting solution weight earlier, discard eluent, 10～30% ethanol elutions that reuse extracting solution weight is 10～50 times are collected this eluent, reclaim under reduced pressure, concentrated, dry promptly gets the purification thing.
4, the preparation method of Radix Paeoniae Rubra injection according to claim 1 is characterized in that the described injection pharmaceutic adjuvant of step (3) is one or more in mannitol, sodium chloride, sorbitol, glucose, fructose, the sodium sulfite.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03139942 CN1225276C (en) | 2003-07-25 | 2003-07-25 | Red peony root injection and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03139942 CN1225276C (en) | 2003-07-25 | 2003-07-25 | Red peony root injection and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1481882A CN1481882A (en) | 2004-03-17 |
| CN1225276C true CN1225276C (en) | 2005-11-02 |
Family
ID=34155163
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03139942 Expired - Fee Related CN1225276C (en) | 2003-07-25 | 2003-07-25 | Red peony root injection and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1225276C (en) |
Families Citing this family (1)
| 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 |
-
2003
- 2003-07-25 CN CN 03139942 patent/CN1225276C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1481882A (en) | 2004-03-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1857664A (en) | Apoplexy treating preparation and its preparing process | |
| CN1927300A (en) | Chinese medicine composition for treating skin pruritus | |
| CN110507708B (en) | Safflower Xiaoyao preparation for treating hyperplasia of mammary glands and preparation method and application thereof | |
| CN110025664B (en) | Pharmaceutical composition for preventing and treating cerebral infarction and/or vascular dementia and application thereof | |
| CN1225276C (en) | Red peony root injection and its preparation method | |
| CN1883533A (en) | Pharmaceutical composition for treating apoplexy and preparation method thereof | |
| CN103893283A (en) | Traditional Chinese medicine composition for treatment of chronic renal diseases and chronic renal failure and its preparation method and use | |
| CN1067901C (en) | Drug for curing migraine and its preparing method | |
| CN1250253C (en) | Chinese medicine capsule for treating ischemic cerebral apoplexy | |
| US12115204B2 (en) | Compound preparation for neuranagenesis, and preparation method therefor and use thereof | |
| CN1861122A (en) | Traditional Chinese medicine prepn. used for treating apoplexia and obstruction of qi in the chest, and its prepn. method | |
| CN104707023A (en) | Traditional Chinese medicinal composition for treating polycystic ovary syndrome, and preparation method thereof | |
| CN1590383A (en) | Rod sage root extract and making method of its preparation | |
| CN1813891A (en) | Perhexiline high-dose injection and its preparing method | |
| CN1176690C (en) | Medicine for treating chronic nephritis | |
| CN1672699A (en) | Medicine for treating phlebothrombosis and thrombotic superficial phlebitis of lower limb and its prepn | |
| CN1557403A (en) | Medicine for treating angiocardiopathy and cerebrovascular disease and its preparing method | |
| CN103083408A (en) | Composition of traditional Chinese medicine extracts, and preparation method and application thereof | |
| CN1559523A (en) | Naodesheng soft capsule and its preparation method | |
| CN1785988A (en) | Saflor yellow pigment rich in saflor yellow pigment B, its preparation method and use | |
| CN1278698C (en) | Freeze dried injection of seeding of autumnal sowthistle-leaf ixeris and preparation method thereof | |
| CN1634241A (en) | Compound formulation of notoginseng for treating cardiovascular and cerebrovascular diseases and its preparing process | |
| CN1817356A (en) | Production of vermilion injection for treating cardiovascular disease | |
| CN1698717A (en) | Chinese medicinal compound fat emulsion injection and its preparation method | |
| EA044900B1 (en) | COMPOUND PREPARATION FOR NERVOUS TISSUE REGENERATION AND METHOD OF ITS PREPARATION AND APPLICATION |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |