Background technology:
Mostly traumatic injury is because of external force or causes from overexerting under fault.As get injured by a fall, wound, contusion, the soft tissue injury due to spraining etc. etc.
Blood circulation promoting and blood stasis dispelling is traditional effective ways of Chinese traditional treatment traumatic injury.Radix Notoginseng is the incised wound key medicine, the hemostasis of tool dissipating blood stasis, the effect of subduing swelling and relieving pain.Be used for spitting of blood, spit blood epistaxis, traumatic hemorrhage, diseases such as tumbling and swelling.The monarch drug of Radix Notoginseng Chang Zuowei injury from falling down medicine, single, compound recipe all can be used as medicine, and as Yunnan BAIYAO, Radix Notoginseng Tabellae, notoginseng injury tablet, pill for traumatic injuries etc. all are the Chinese medicine compound preparation of monarch drug with the Radix Notoginseng.The blood circulation promoting and blood stasis dispelling active component of Radix Notoginseng is that (Panax notoginoside PNS), has the hemorheology of improvement and microcirculatory effect to Radix Notoginseng total arasaponins, and antiplatelet aggregation and antithrombotic effect are arranged, and pain relieving, antiinflammatory, bacteriostasis are still arranged.Radix Notoginseng total arasaponins preparation such as XUESAITONG PIAN, capsule, injection are still being brought into play crucial effects in Bone injury disease except that the treatment that is widely used in cardiovascular and cerebrovascular disease.[Zhao Yuhang. XUESAITONG is used at the orthopaedic disease initial stage and is known from experience. Yunnan Chinese medicine magazine, 1997,18 (1): 49; Zhang Chunyu etc. the discussion of Radix Notoginseng clinical practice and mechanism of action. Heilungkiang medical science, 2001,25 (11): 842].
Herba Centellae tool clearing away heat-damp and promoting diuresis, the effect of removing toxic substances and promoting subsidence of swelling is used for jaundice due to damp-heat, heatstroke diarrhoea, sand Stranguria stranguria with blood, carbuncle sore tumefacting virus, injury from falling down.Herba Centellae external and existing more than the 2000 year history of curing the disease for oral administration.Modern study shows, the triterpenoid saponin composition that from Herba Centellae, extracts, can promote wound healing, stimulate the granulation growth, promote the epidermis keratinization, and help to take place new connective tissue, extensively treat various wounds, burn wound, the cicatrix that acne and plastic and aesthetic surgery etc. causes, keloid and scleroderma.[asiaticoside sheet description; Zhang Tao etc., the influence that asiaticoside is expressed cyclin, proliferating cell nuclear antigen in the burn wound healing, Chinese experimental surgery magazine, 2005,22 (1): 43; Xu Hao etc., Herba Centellae Pharmacological action study, aminoacid and living resources, 2005,27 (2): 17].
Existing investigative technique does not have compound recipe or the relevant report that pseudo-ginseng activity composition Radix Notoginseng total arasaponins and Herba Centellae active component Herba Centellae total glycosides are made up.
Summary of the invention:
The objective of the invention is to develop a kind of prescription and simplify, effective ingredient is clear and definite, and drug effect is definite, quality controllable and the Radix Notoginseng total arasaponins that side effect is low and the pharmaceutical composition of Herba Centellae total glycosides.
Another object of the present invention is to this pharmaceutical composition and can be used for preparing application in the medicine for the treatment of traumatic injury.
The pharmaceutical composition that a kind of Radix Notoginseng total arasaponins and Herba Centellae total glycosides are formed, its weight ratio is 2~20:1; Its optimum weight ratio is 4~10:1.
Prescription foundation of the present invention: Radix Notoginseng total arasaponins is a blood circulation promoting and blood stasis dispelling active component in the Chinese medicine Radix Notoginseng, has the hemorheology of improvement and microcirculatory effect, and effects such as antiplatelet aggregation and antithrombotic formation are arranged.Herba Centellae total glycosides is an active component in the Chinese medicine Herba Centellae, can promote wound healing, stimulates the granulation growth, promotes the epidermis keratinization, and helps to take place new connective tissue.Radix Notoginseng total arasaponins is longer than promoting blood circulation to remove blood stasis, and Herba Centellae total glycosides is longer than wound healing, and two medicines share, and has complementary advantages tool promoting blood circulation to remove blood stasis, the effect of antalgic and inflammation relieving and promotion wound healing.Can be used for making the medicine of treatment traumatic injury.
Pharmacodynamic study is as follows:
Experiment 1: to the facilitation of mice ecchymosis absorption
This experiment is adopted and is given the quantitative self-blood of mice cervical region subcutaneous injection, causes the ecchymosis model, judges the elimination absorbing state of hematoma by the weight of weighing hematoma piece, thereby reflects the function of promoting blood circulation to disperse blood clots of medicine.Get 50 of Kunming mouses, male and female half and half, body weight 25 ± 2g.Be divided into 5 groups at random by the sex body weight, every group 10, be respectively blank group (0.8%CMC-Na), positive drug control group (3 of FUFANG DANSHEN DIWAN/kg), Radix Notoginseng total arasaponins group (50mg/kg), Herba Centellae total glycosides group (5mg/kg), compositions group (and Radix Notoginseng total arasaponins and asiatic centella total glycoside composition, 55mg/kg).Cause self hematoma model before the experiment earlier, promptly get blood from eye socket respectively, splash into and be placed with 0.1ml CaCl in advance
2(every ml contains the 0.1M CaCl of penicillin 100,000 units to solution
2Solution) to the 0.5ml scale, jolting is even in the small test tube, extracts the back from the subcutaneous injected in mice that gives with syringe rapidly, forms ecchymosis.Cause beginning administration in second day behind the model, each medicine all is mixed with respective concentration with the 0.8%CMC-Na suspension, gives mouse stomach.Administration 7 days is put to death the mice dislocation of cervical vertebra after 1 hour in the last administration, and the residual hematoma piece that mice nape place is subcutaneous is separated, weigh with electronic scale, reflect the medicine function of promoting blood circulation to disperse blood clots according to residual hematoma piece weight, medication group and blank group statistical, t check between the employing group.The results are shown in Table 1.
The influence that table 1. pair mice ecchymosis absorbs
Compare * P<0.05, * * P<0.01 with the blank group
By table 1 as seen, Radix Notoginseng total arasaponins and asiatic centella total glycoside composition and Radix Notoginseng total arasaponins all can significantly reduce mouse experiment ecchymosis weight, effect and FUFANG DANSHEN DIWAN are suitable, but the independent use of asiaticoside does not have this effect, the blood circulation invigorating efficacies that compositions has been described is to have brought into play the length of the effect of invigorating blood circulation of Radix Notoginseng total arasaponins, has replenished the corresponding insufficient result of asiaticoside.
Experiment 2: mice analgesic experiment
Kunming mouse, male and female half and half, 18-21g, is divided into 5 groups at random by 50, every group 10, be respectively blank group, positive drug control group (3 of FUFANG DANSHEN DIWAN/kg), Radix Notoginseng total arasaponins group (50mg/kg), Herba Centellae total glycosides group (5mg/kg), compositions group (and Radix Notoginseng total arasaponins and asiatic centella total glycoside composition, 55mg/kg), behind the administration 30min, the acetic acid 0.1ml/10g of the equal ip of each treated animal injection 0.6% observes mouse writhing number of times in back 15 minutes of injection.Carry out the analysis of t inspection statistics by administration group and blank group, the results are shown in Table 2.
Table 2. pair mice acetic acid causes the inhibitory action of pain reaction
Compare * P<0.05, * * P<0.01 with the blank group
By table 2 as seen, Radix Notoginseng total arasaponins, Herba Centellae total glycosides all have better analgesic activity, and the analgesic activity of the two compositions then significantly strengthens.
Experiment 3: suppress the scorching experiment of Mice Auricle caused by dimethylbenzene xylene
Kunming mouse, male, 23 ± 2g, 50, be divided into 5 groups at random, every group 10, be respectively blank group, positive drug control group (indomethacin, 20mg/kg), Radix Notoginseng total arasaponins group (50mg/kg), Herba Centellae total glycosides group (5mg/kg), compositions group (Radix Notoginseng total arasaponins and asiatic centella total glycoside composition, 55mg/kg), each CMC-Na solution of medicinal 0.5% is made into suspension, gastric infusion, the administration volume is 10ml/kg, and gastric infusion is 5 days continuously, every day 1 time, wherein the blank group is irritated stomach and is given isopyknic 0.5%CMC-Na solution.1h after the last administration, each auris dextra tow sides dropping xylene solution 30 μ l that organize mice causes inflammation.Take off cervical vertebra behind the 2h and put to death each mice, lay round auricle with the card punch of diameter 7mm respectively at its same position of left and right sides ear, weigh, calculate the weight difference of two ears, be the swelling degree, each administration group and blank group are relatively carried out the analysis of t inspection statistics, the results are shown in Table 3.
The influence of table 3. xylol induced mice auricle edema
Compare * P<0.05, * * P<0.01 with the blank group
By table 3 as seen, Radix Notoginseng total arasaponins, Herba Centellae total glycosides all have better antiinflammatory action, and the antiinflammatory action of the two compositions then significantly strengthens.
Experiment 3: promote the experiment of wound healing effect
Kunming mouse, male and female half and half, 25 ± 2g, 40, be divided into 4 groups at random, 10 every group, be respectively blank model control group, Radix Notoginseng total arasaponins group (50mg/kg), Herba Centellae total glycosides group (5mg/kg), compositions group (Radix Notoginseng total arasaponins and asiatic centella total glycoside composition, 55mg/kg).Before the experiment mice is caused the wound model, promptly with shears cut off the mouse back hair (15mm * 5mm), standardized dark wound of the long 1mm of 10mm of usefulness scalpel, wound dressing is good.Beginning administration in second day after the modeling, each CMC-Na solution of medicinal 0.5% is made into suspension, gastric infusion, the administration volume is 10ml/kg, and gastric infusion is 4 days continuously, and every day 1 time, its empty model control group is irritated stomach and is given isopyknic 0.5%CMC-Na solution.1h after the last administration, the length of measurement mice wound healing is the healing degree, and each administration group and blank model control group are relatively carried out the analysis of t inspection statistics, the results are shown in Table 4.
The influence of table 4. pair mice wound healing
Compare * P<0.05, * * P<0.01 with model control group
By table 4 as seen, Radix Notoginseng total arasaponins and asiatic centella total glycoside composition and Herba Centellae total glycosides all can significantly promote wound healing, but the independent use of Radix Notoginseng total arasaponins does not have this effect, the promotion wound healing effect that compositions has been described is a length of having brought into play the effect of Herba Centellae total glycosides, has replenished the corresponding insufficient result of Radix Notoginseng total arasaponins.
Brief summary: the result of experiment 1-4 shows, the compositions tool promoting blood circulation to remove blood stasis of Radix Notoginseng total arasaponins and Herba Centellae total glycosides, and the effect of antalgic and inflammation relieving and promotion wound healing, and better than the only result of use of two prescriptions, can be used for making the medicine for the treatment of traumatic injury.
The specific embodiment:
Embodiment 1:
The preparation of Radix Notoginseng total arasaponins: get pseudo-ginseng and be ground into coarse powder 1000g, add 70% ethanol of 8 times of medical material weight, reflux, extract, 3 times, extract 2 respectively, 2,1 hour, filter merge extractive liquid,, reclaim ethanol to there not being alcohol, and be condensed into the aqueous solution of 1g crude drug/ml, through ethyl acetate, water-saturated n-butanol respectively extracts 3 times, gets n-butanol layer, the reclaim under reduced pressure n-butyl alcohol is done near, add the small amount of methanol dissolving, in methanol solution, add acetone again, separate out precipitation, filter, get precipitation, drying is pulverized, cross 55 mesh sieves, promptly get sundown Radix Notoginseng total arasaponins finished product, weight is 28g, and content of the total saponins in radix notoginseng is 64.5%.
The preparation of Herba Centellae total glycosides: get Herba Centellae 1000g, add 80% ethanol of 20 times of medical material weight, reflux, extract, 3 times, extract 2 respectively, 2,1 hour, filter merge extractive liquid,, reclaim ethanol to there not being alcohol, and be condensed into the aqueous solution of 1g crude drug/ml, through petroleum ether, ethyl acetate, water-saturated n-butanol respectively extracts 3 times, gets n-butanol layer, the reclaim under reduced pressure n-butyl alcohol is done near, add the small amount of methanol dissolving, in methanol solution, add acetone again, separate out precipitation, filter, get precipitation, drying is pulverized, cross 55 mesh sieves, promptly get yellow Herba Centellae total glycosides finished product, weight is 10.8g, and Herba Centellae total glycosides content is 56.5%.
Embodiment 2:
Get embodiment 1 Radix Notoginseng total arasaponins 5g, Herba Centellae total glycosides 0.25g adds starch 5g, mix homogeneously, the back filled capsules or make tablet of granulating.
Embodiment 3:
Get embodiment 1 Radix Notoginseng total arasaponins 5g, Herba Centellae total glycosides 0.5g adds starch 5g, mix homogeneously, the back filled capsules or make tablet of granulating.
Embodiment 4:
Get embodiment 1 Radix Notoginseng total arasaponins 5g, Herba Centellae total glycosides 0.6g adds starch 5g, mix homogeneously, the back filled capsules or make tablet of granulating.
Embodiment 5:
Get embodiment 1 Radix Notoginseng total arasaponins 5g, Herba Centellae total glycosides 1g adds starch 5g, mix homogeneously, the back filled capsules or make tablet of granulating.
Embodiment 6:
Get embodiment 1 Radix Notoginseng total arasaponins 5g, Herba Centellae total glycosides 2.5g adds starch 5g, mix homogeneously, the back filled capsules or make tablet of granulating.