CN1457852A - A Chinese medicinal composition for treating traumatic injury and pain in chest and hypochondrium, and its preparation method - Google Patents
A Chinese medicinal composition for treating traumatic injury and pain in chest and hypochondrium, and its preparation method Download PDFInfo
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- CN1457852A CN1457852A CN 03131143 CN03131143A CN1457852A CN 1457852 A CN1457852 A CN 1457852A CN 03131143 CN03131143 CN 03131143 CN 03131143 A CN03131143 A CN 03131143A CN 1457852 A CN1457852 A CN 1457852A
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- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- GTHUJPJMPAQNJI-UHFFFAOYSA-H tricalcium sulfuric acid diphosphate Chemical compound P(=O)([O-])([O-])[O-].[Ca+2].S(O)(O)(=O)=O.P(=O)([O-])([O-])[O-].[Ca+2].[Ca+2] GTHUJPJMPAQNJI-UHFFFAOYSA-H 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
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Abstract
The invention discloses a Chinese medicinal composition for treating traumatic injury and chest and hypochondrium pain, a preparation method and a quality control method thereof. The composition comprises radix et rhizoma Rhei preparata, radix Angelicae sinensis, bupleuri radix, Trichosanthis radix, semen Persicae, Carthami flos, rhizoma corydalis, and Glycyrrhrizae radix. The preparation of the Chinese medicinal composition adopts methods of decoction and ethanol extraction, so as to fully exert the effective medicaments, and the invention also provides a quality control method for carrying out component identification and content measurement on the composition. The composition of the invention has good effect on treating traumatic injury and pain in chest and hypochondrium.
Description
Invention field
The present invention relates to a kind of Chinese medicine composition, particularly treatment traumatic injury, the Chinese medicine composition of pain in chest and hypochondrium relates to the preparation method and the method for quality control of said composition simultaneously.
Background technology
Traumatic injury comprises soft tissue injury, fracture, internal injury.
Soft tissue injury: the contusion of the breast side of body, thoracic wall contusion, contusion of abdominal wall, traumatic pleuritis, wound aphonia, brothers sprain, lumbar sprain, wound hematoma, traumatic ulcer;
Fracture: extremity fracture, fracture of rib merges pneumothorax, hemothorax, pneumohemothorax, and os pelvicum fracture merges pelvic hematoma;
Internal injury: cerebral concussion, subdural hematoma, hepatic injury, splenic trauma, injury of kidney.
Summary of the invention
One object of the present invention is to disclose a kind of new treatment traumatic injury, pain in chest and hypochondrium Chinese medicine composition; Another object of the present invention is a kind of new treatment traumatic injury of open preparation, the method for pain in chest and hypochondrium Chinese medicine composition; The object of the invention also is to disclose a kind of method of quality control of new Chinese medicine composition.
The crude drug of pharmaceutical composition of the present invention is formed and proportioning following (by weight):
Radix Et Rhizoma Rhei 360-400 weight portion Radix Angelicae Sinensis 280-320 weight portion
Radix Bupleuri 280-320 weight portion Radix Trichosanthis 280-320 weight portion
Semen Persicae 200-250 weight portion Flos Carthami 200-250 weight portion
Rhizoma Corydalis 200-250 weight portion Radix Glycyrrhizae 130-170 weight portion.
The preferred Semen Persicae (peeled) of described Semen Persicae, the preferred vinegar Rhizoma Corydalis of Rhizoma Corydalis.
This preparation of drug combination method:
More than eight flavors, add 13-17 times of water gaging and soak and decoct 35-55 minute at every turn 1-3 time, collecting decoction filters, and filtrate is concentrated into 15-25 ℃ of relative density 1.00～1.05, adding ethanol makes the alcohol amount of containing reach 25-35%, left standstill 10-14 hour, and filtered filtrate recycling ethanol, be concentrated into the extractum shape, drying, through conventional operation directly or add pharmaceutically acceptable excipient and make clinical acceptable forms, as tablet, oral liquid, capsule, granule etc.
The method of quality control that this compositions is made medicament comprises discriminating and/or assay.
Discrimination method: comprise a kind of and/or several in the following method: a. gets this composite preparation 2g, adds methanol 30ml supersound process 10-20 minute, filters, and filtrate is concentrated into about 2ml, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 1g, gets control medicinal material solution with legal system; Get the emodin reference substance again, add methanol and make the solution that contains 0.1mg among every 1ml, in contrast product solution; According to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B) test, draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, and takes out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color respectively; B. get this composite preparation 4g, add methanol 40ml, supersound process 15-25 minute, filter, the filtrate evaporate to dryness, residue adds water 20ml makes dissolving, adds dilute hydrochloric acid and transfers about pH value to 2, uses ether extraction 3 times, merge ether extracted liquid, extract 3 times with 2% sodium carbonate liquor, divide the water intaking layer, with ethyl acetate 15ml washing, discard the ethyl acetate washing liquid, transfer pH value to 2～3 with salt,, discard benzene liquid with benzene 15ml washing, continue and use ether extraction 3 times, ether extracted liquid evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography solution (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B), draw need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, and takes out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical navy blue fluorescence speckle; C. get this composite preparation 4g, add methanol 30ml supersound process 10-20 minute, filter, filtrate evaporate to dryness, residue add water 20ml makes dissolving, enriching ammonia number droplet is transferred more than the pH value to 9, with ether extraction 1-3 time, each 20ml merges ether solution, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 1mg among every 1ml, in contrast product solution, test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B), draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with 6-8.5: 3-5: 1-2 normal hexane-chloroform-methanol is developing solvent, launch, take out, dry, put smoke in the iodine steam after, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; Assay: get this composite preparation 2g, the accurate title, decide, put in the apparatus,Soxhlet's, it is an amount of to add methanol, heating and refluxing extraction, to extracting liquid colourless, extracting solution reclaims methanol to doing, and residue adds water 50ml, transfers pH value to 2～3.5 with rare HCl, put in the 85-95 ℃ of water-bath hydrolysis 1-3 hour, hydrolyzed solution quantitatively is transferred in the separatory funnel, adds diethyl ether to extract 7-9 time, each 50ml, merge extractive liquid,, reclaim ether to doing, residue adds dehydrated alcohol and quantitatively is transferred in the 5ml volumetric flask, adds dehydrated alcohol to scale, shake up, as need testing solution; Other gets the emodin reference substance, adds dehydrated alcohol and makes the solution that contains 0.1mg among every 1ml, in contrast product solution; Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B), draw need testing solution 5 μ l, reference substance solution 2 μ l and 4 μ l, put respectively on same silica gel g thin-layer plate, with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, and takes out, dry, carry out scanning wavelength λ according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B thin layer chromatography scanning)
s=420nm, λ
R=550nm measures test sample trap integrated value and reference substance trap integrated value, calculates, promptly; This composite preparation per unit amount contains Radix Et Rhizoma Rhei by emodin (C
15H
10O
5) meter, must not be less than 0.030-0.038mg.
Above-mentioned unit quantity is meant the finished medicines dosage that contains suitable 2.12g crude drug.
The present composition has good blood circulation promoting and blood stasis dispelling, and the promoting the circulation of QI to relieve pain effect has analgesia, antiinflammatory, anticoagulant, antithrombotic, blood viscosity lowering, promotion absorption of hematoma, blood vessel dilating, microcirculation improvement, repairs effects such as damage, oral safety.On preparation, technical maturity, steady quality.Following experimental example is used to further specify the present invention.Experimental example 1 pharmacodynamics test
1. be subjected to the reagent thing: this composite preparation (Capsule for treating wound) is provided lot number 930917 by China Medicine University Chinese medicine preparation research department.Get capsule 's content before the experiment, adding distil water is an amount of, is heated to little boiling on the electric furnace, makes capsule 's content dissolving, is cooled to room temperature, and compound concentration was 100% (every ml contains medical material 1g), for irritating stomach with (calling grieved liquid in the following text).
Positive control drug: (1) notoginseng injury tablet water extract (calling Radix Notoginseng liquid in the following text).Notoginseng injury tablet is the compound Chinese medicinal preparation (Shandong defend the accurate word of medicine＜87〉334-11 number) of state approval, cures mainly contusion, sprains etc., has listed national essential drugs in.Get notoginseng injury tablet (Kangping, Yantai pharmaceutical factory, lot number 930430) levigation before the experiment, adding distil water electric heating boils, and is mixed with 15% concentration (every ml contains tablet labelled amount 0.15g), uses for irritating stomach.This research at analgesia, antiinflammatory, anticoagulant, hematoma model, dampen in the test such as model with the positive contrast of Radix Notoginseng liquid.2. TONGSAIMAI PIAN water extract (calling TONGSAIMAI liquid in the following text).TONGSAIMAI PIAN is the compound Chinese medicinal preparation (the accurate word of Su Wei medicine＜82〉1638-1 number) of state approval, cures mainly angiopathy such as thromboangiitis obliterans, has listed national essential drugs in.Get TONGSAIMAI PIAN (pharmaceutical factory of Nanjing Traditional Chinese Medical College, 940316) levigation before the experiment, adding distil water electric heating boils, and is mixed with 100% concentration (every ml contains tablet labelled amount 1g), uses for irritating stomach.This research in tests such as blood viscosity, thrombosis, blood vessel perfusion, microcirculation with the positive contrast of TONGSAIMAI liquid.
Other medicine and reagents: antimony potassium tartrate, Chengdu chemical reagent factory, lot number: 890526.Calcium chloride, Xing Ta chemical plant, Kingsoft, Shanghai, 901124.Carrageenin, Oleum Tiglii, Shenyang Pharmacy College institute of materia medica provides.Heparin sodium, China Drug Co.'s Beijing purchasing and supply station sells 900702.Thrombin, biochemical-pharmaceutical factory, Shanghai, 9408101.Penicillin, Lukang Medicine (Group) Co. Ltd., Shandong Prov., B930913.Formalin, Nanjing chemical reagent factory, 890806.
2. laboratory animal: Kunming kind white mice, SD rat are provided by China Medicine University's Experimental Animal Center.The quality certification: No. the 93012nd, moving (matter) word of Soviet Union.Size of animal, body weight, sex and pathology moulding etc. specify in every test.
3. test method and result
3.1 analgesic test
3.1.1 the test of antimony potassium tartrate writhing response: 50 of mices, male, 18～22g is divided into 5 groups at random.3 administration groups are distinguished the grieved liquid 5g/kg of ig, 10g/kg, 20g/kg, blank group ig normal saline (NS), and positive controls ig Radix Notoginseng liquid 3g/kg all irritates stomach with isometric(al).Each organizes 1h after the mice administration, and every Mus ip0.05% antimony tartrate potassium solution 0.4ml/ only observes and writes down every Mus and occur turning round the body number of times in time (incubation period) of writhing response and the 10min
[1]The results are shown in Table 1.
Group n dosage (g/kg) incubation period of influencing that table 1 paratartaric acid antimony potassium causes pain, (S, X ± SD) turned round body number of times (NS 10 127.9 ± 59.9 16.1 ± 6.1 Radix Notoginseng liquid 10 3 236.5 ± 24.3 of X ± SD)
* *9.6 ± 2.3
* *Grieved liquid 10 20 262.7 ± 45.6
* *7.7 ± 4.7
* *
10 10 219.3±21.2
*** 10.2±2.3
***
10 5 152.3±26.9
* 12.7±2.7
*
T check (down together), with NS group ratio,
* *P＜0.01,
*P＞0.05
By table 1 as seen, mice is taken grieved liquid, and writhing response significant prolongation incubation period is turned round the body number of times and significantly reduced.
3.1.2 electricity irritation causes the pain test
Male mice, 18～22g carries out the sensitivity screening earlier before the experiment
[2]: 8V, 1HZ, the 0.05S square wave of using instrument (YSD-5 type, Bangbu radio two factories) to produce with pharmacology physiology stimulate more, and the responder that occurs shouting in 30S is qualified for screening.Get 50 of the qualified mices of sensitivity, be divided into 5 groups at random.3 administration groups are distinguished the grieved liquid 5g/kg of ig, 10g/kg, 20g/kg, blank group ig isometric(al) normal saline, positive controls ig Radix Notoginseng liquid 3g/kg.1h after each Mus administration, the same method electricity irritation causes pain, writes down the incubation period that every Mus electricity irritation is shouted and reacted.The results are shown in Table 2.
Table 2 pair electricity irritation causes the influence of pain
Incubation period (S, the group n dosage (g/kg) of X ± SD)
NS 10 8.5 ± 1.6 6.8 ± 2.5 after the administration before the administration
△Radix Notoginseng liquid 10 3 9.6 ± 2.3
*56.4 ± 12.7
△ △ △ * *Grieved liquid 10 20 8.8 ± 2.3
*72.3 ± 23.6
△ △ △ * *
10 10 9.2±3.0
* 46.8±11.4
△△△ ***
10 5 8.4±2.3
* 47.5±11.1
△△△ ***
With NS group ratio,
*P＞0.05,
* *P＜0.01
With ratio before the administration,
△P＞0.05,
△ △ △P＜0.01
By table 2 as seen, mice is taken grieved liquid, and electricity irritation causes significant prolongation incubation period of pain.Above-mentioned 2 experimental results show, grieved liquid causes pain and electricity irritation to chemistry and causes pain and react remarkable inhibitory action is arranged.
3.2 antiinflammatory test
3.2.1 rat paw edema test
40 of male rats, body weight 240～280g is divided into 5 groups at random.3 administration groups are distinguished the grieved liquid 5g/kg of ig, 10g/kg, 20g/kg, blank group ig isometric(al) water, positive controls ig Radix Notoginseng liquid 3g/kg.1h after the administration, with screw micrometer measure right back sufficient sole of the foot thickness as cause scorching before thickness, and at right back sufficient sole of the foot metacarpus SC1% chondrus ocellatus Holmes glue 0.1ml so that scorching, cause scorching back 1h, 3h, 6h measures right back sufficient sole of the foot thickness respectively, with cause scorching before thickness relatively, calculate the pedal swelling rate.The results are shown in Table 3.
The influence of table 3 pair rat carrageenan foot swelling
Cause scorching front foot sole of the foot thickness pedal swelling rate (%, the group n dosage (g/kg) of X ± SD)
(mm, x ± SD) cause 1h 3h 6h NS 8 2.898 ± 0.226 36.4 ± 9.4 49.7 ± 12.8 36.7 ± 10.7 Radix Notoginseng liquid 83 2.690 ± 0.153 26.2 ± 8.4, scorching back
*42.8 ± 11.4
*31.6 ± 9.1
*Grieved liquid 8 20 2.737 ± 0.164 23.3 ± 8.1
* *35.1 ± 7.8
* *23.9 ± 6.8
* *
8 10 2.946±0.307 27.7±7.4
***?37.3±9.2
*** 27.2±8.5
***
8 5 2.769±0.240 28.0±6.7
***?39.8±7.7
* 29.5±6.3
**
With NS group ratio,
*P＞0.05,
*P＜0.05,
* *P＜0.01
By table 3 as seen, grieved liquid is oral, and the swelling rate of rat carrageenan pedal swelling is significantly reduced.3.2.2 mice auricle swelling test
50 of male mices, body weight 25～30g is divided into 5 groups at random.The same analgesic test of dosage.Each is organized after irritating stomach 1h, causes scorching liquid 0.1ml with 2% compound Oleum Tiglii and is applied to the left auricle of every Mus and causes inflammation
[4]Cause scorching RGK 4h and take off cervical vertebra and put to death mice, cut two ears, in lay the garden auricle with the position, electronic balance (TMP-1 type, Hunan instrument balance equipment factory) is weighed with the 9mm card punch, with the ratio (%) of left and right sides auricle weight difference and auris dextra sheet weight as scorching ear swelling rate.The results are shown in Table 4.
Heavily (mg, x ± SD) the auris dextra sheet is heavy for the left auricle of group n dosage (g/kg) that influences of table 4 pair Mus otitis swelling
Scorching ear swelling rate
NS 10 16.9 ± 1.4 6.2 ± 0.8 173.0 ± 42.0 Radix Notoginseng liquid 10 3 14.2 ± 2.4 6.0 ± 0.7 135.2 ± 23.6
*Grieved liquid 10 20 12.8 ± 1.7 6.8 ± 1.0 89.9 ± 21.7
* *
10 10 13.2±1.6 5.9±0.7 124.7±20.9
***
10 5 14.0±2.4 6.1±0.9 132.1±21.0
**
With NS group ratio,
*P＜0.05,
* *P＜0.01
By table 4 as seen, grieved liquid is oral, and the mouse knoting oil auricle edema is significantly reduced.Above-mentioned 2 experiments show that grieved liquid has resist inflammation on repercussive function.
3.3 blood circulation promoting and blood stasis dispelling test
3.3.1 coagulation time test: 40 of mices, male and female half and half, body weight 18～22g is divided into 4 groups at random.2 the grieved liquid 10g/kg of administration group difference ig, 20g/kg, blank group ig isometric(al) normal saline, positive controls ig Radix Notoginseng liquid 3g/kg.1h behind the filling stomach, every rathole rear vein beard is got blood, measures clotting time (CT) with capillary glass-tube method.Experimental result sees Table 5.
Table 5 pair clotting time of mice influence group n dosage (g/kg) CT (S, NS 10 75.6 ± 18.8 Radix Notoginseng liquid 10 3 283.5 ± 42.3 of X ± SD)
* *Grieved liquid 10 20 316.2 ± 36.3
* *
10 10 199.7±22.2
***
With NS group ratio,
* *P＜0.01
By table 5 as seen, grieved liquid is oral, the clotting time of mice significant prolongation.
3.3.2 thrombin time test:
Mice source, grouping, administration are the same, successive administration 3 days, and 1h after the last administration plucks eyeball and gets blood, and centrifuging and taking blood plasma (Disodium oxalate. anticoagulant) 0.1ml puts in 37 ℃ of water-baths, adds the thrombin solution 0.1ml for preparing, record thrombin time (TT).The results are shown in Table 6.
Table 6 pair mice thrombin time influence group (the n dosage of g/kg * d) (S, TT NS 10 18.3. ± 5.8 Radix Notoginseng liquid 10 3 * 3 27.8 ± 8.3 of X ± SD)
* *Grieved liquid 10 20 * 3 29.3 ± 7.5
* *
10 10×3 25.7±6.2
**
With NS group ratio,
*P＜0.05,
* *P＜0.01
By table 6 as seen, mice is taken grieved liquid, the thrombin time significant prolongation.3.3.3 blood plasma recalcification time: go up a mice anticoagulate plasma 0.1ml of test (3.3.2), add the CaCl that configures
2Solution 0.1ml, the record white particle time of separating out is blood plasma recalcification time (RT).The results are shown in Table 7.
Table 7 pair mice plasma recalcification time influence group n dosage (RT of g/kg * d) (S, NS 10 32.7. ± 6.5 Radix Notoginseng liquid 10 3 * 3 55.8 ± 13.2 of X ± SD)
* *Grieved liquid 10 20 * 3 57.5 ± 12.8
* *
10 10×3 49.3±9.3
***
With NS group ratio,
* *P＜0.01
By table 7 as seen, mice is taken grieved liquid, blood plasma recalcification time significant prolongation.More than 3 result of the tests show that grieved liquid has significant anticoagulation.
3.3.4 blood viscosity is measured: 32 of rats, 180～220g, male and female half and half.Every Mus is got blood and surveys whole blood and plasma viscosity before the administration, is divided into 4 groups at random, and 8 every group, male and female half and half make that respectively to organize rat blood viscosity average before the administration close.2 the grieved liquid 10g/kg of administration group difference ig, 20g/kg, positive controls ig TONGSAIMAI liquid 10g/kg, blank group ig isometric(al) normal saline, every day 1 time, continuous 7 days.1h after the last administration, whole blood and plasma viscosity after the administration of the same method mensuration.The results are shown in Table 8.Blood viscosity is measured and is adopted capillary tube method
[8]: the rat eye socket is got the about 4ml of blood, puts into the silication test tube of handling with heparin in advance, makes into anticoagulation, leaves standstill 10min, surveys whole blood contrast viscosity with blood viscometer (L-100 type, Shanghai Medical Univ).The residue anticoagulation is centrifugal, gets supernatant, surveys plasma viscosity.
The influence of table 8 pair rat blood viscosity
Dosage whole blood contrast viscosity (shear rate 1/s, the plasma viscosity group n of X ± SD)
(g/kg * d) 80 60 40 30 20 (NS 8 medicines preceding 7.40 ± 0.68 8.18 ± 1.21 8.50 ± 0.79 9.60 ± 1.26 10.50 ± 1.20 1.75 ± 0.21 of X ± SD)
Behind the medicine 7.65 ± 10.36
△8.51 ± 0.41
△9.09 ± 0.43
△9.93 ± 10.55
△10.67 ± 0.71
△1.74 ± 0.12
△TONGSAIMAI liquid 8 10 * 7 medicines preceding 7.37 ± 0.88 8.10 ± 0.92 9.03 ± 1.06 9.97 ± 1.14 10.73 ± 1.10 1.65 ± 0.05
6.44±0.94
△△△* 6.93±1.05
△△△ 1.60±0.06
△
Behind the medicine 5.98 ± 0.88
△ △ △* * 7.57 ± 1.14
△ △ △* * 8.18 ± 1.28
△ △ △* *
Grieved liquid 8 20 * 7 medicines preceding 7.58 ± 0.94 8.18 ± 1.12 8.66 ± 1.25 9.28 ± 1.55 10.19 ± 1.32 1.67 ± 0.07 of * * * * *
6.84±0.65
△△△* 7.43±0.78
△△*
Behind the medicine 6.16 ± 0.58
△ △ △* * 8.45 ± 0.76
△ △* * 8.83 ± 0.94
△ △* * 1.61 ± 0.08
△*
** **
8 10 * 7 medicines preceding 7.33 ± 0.23 8.14 ± 0.25 8.78 ± 0.36 9.45 ± 0.44 10.31 ± 1.00 1.75 ± 0.08
7.49±0.70
△△△*
Behind the medicine 6.64 ± 0.68
△ △ △* 8.16 ± 0.89
△* 8.83 ± 1.08
△* 9.83 ± 1.28
△* 1.70 ± 0.09
△*
*
Self compares before and after the administration,
△P＞0.05,
△ △P＜0.05,
△ △ △P＜0.01
Organize ratio, * P＞0.05, * * P＜0.05, * * * P＜0.01 with NS after the administration
By table 8 as seen, rat is taken grieved liquid, and whole blood viscosity significantly reduces, and there were significant differences with normal saline group ratio.
3.3.5 thrombotest: 40 of rats, 180～220g, male and female half and half.Form thrombosis with the arteriovenous shut method: with the urethane intraperitoneal anesthesia, separate right common carotid artery and left external jugular vein, be communicated with, form arteriovenous shut with the polyethylene tube of inserting the 5cm silk thread.30min behind the gastric infusion, open blood flow 15min gets the silk thread scales/electronic balance weighing.Gross weight deducts silk thread and heavily is thrombus weight.The results are shown in Table 9.
Table 9 pair rat suppository forms influences group n dosage (g/kg) thrombosis heavy (mg, suppression ratio (%) NS 8 31.8 ± 6.6 Radix Notoginseng liquid 8 10 19.2 ± 5.9 of X ± SD)
* *39.6 grieved liquid 8 20 17.6 ± 5.3
* *44.7
8 10 18.4±6.3
*** 42.1
8 5 20.2±5.8
*** 36.5
With NS group ratio,
* *P＜0.01
By table 9 as seen, grieved liquid has remarkable inhibitory action to thrombosis.
3.3.6 rat hindlimb blood vessel perfusion experiment: 24 of rats, male and female half and half, body weight 250～300g is divided into 4 groups, the reference literature method at random
[10]The stripped hind leg blood vessel perfusion specimen of preparation, abdominal aortic cannulation, Rockwell liquid perfusion, effluent writes down flow with drop recorder.Grieved liquid and TONGSAIMAI liquid, inject in the perfusate from the arterial cannulation top with refining with the buchner funnel sucking filtration, before the record administration and after the administration the 5th, 10,15, the flow of 20min, with drip/minute/(g/min) expression, the results are shown in Table 10.
The influence of table 10 pair rat hindlimb blood vessel perfusion flow
Net added value behind the dosed administration prodrug (g/min, the group n of X ± SD)
(concentration, volume) (g/min, 5min 10min 15min 20min NS 6 0.2ml 40.2 ± 8.1 3.0 ± 1.50 2.5 ± 1.4 2.0 ± 1.3 1.3 ± 0.5 of X ± SD)
7.5 ± 2.5
*9.0 ± 2.2
*7.2 ± 1.8
*5.8 ± 2.2
*TONGSAIMAI liquid 6 100%-0.2ml 39.2 ± 7.1
** * * * * * *
10.6 ± 2.8 13.0 ± 3.2 11.5 ± 2.8 7.6 ± 1.5
*Grieved liquid 6 100%-0.2ml 38.7 ± 9.9
** * * * * * * * * *
5.3±1.8
* 4.3±1.2
*
6 100％-0.1ml 41.0±12.2
* * * 3.2±1.3
* 1.0±1.3
*
With NS group ratio,
*P＞0.05,
*P＜0.05,
* *P＜0.01
By table 10 as seen, grieved liquid significantly increases rat hindlimb blood vessel perfusion flow, and showing has the effect of expansion peripheral blood vessel.
3.3.7 the test of Mice Auricle microcirculation: 40 of mices, male and female half and half, 18～22g is divided into 4 groups at random.2 the grieved liquid 10g/kg of administration group ig, 20g/kg, blank group ig isometric(al) water, positive controls ig TONGSAIMAI liquid 10g/kg.Observe with OLYMPUS-BH type microcirculation microscope: ip in mice urethane 25%-0.1ml/10g anesthesia, lie on one's side on the lucite brassboard, one exterior feature of picking up the ears is equipped with in the holder of machine glass ear, drip coating liquid paraffin, put microscopically, amplify 100X, the printing opacity light source selects the suitable visual field (arteriole, venule companion row) to observe.Index: 1. auricle arteriole, venule caliber, before medicine and behind the medicine 10,20,40min surveys 4 times altogether; 2. color and fluidised form.
Laboratory observation arrives, Mice Auricle arteriole blood flow is the pale red linear flow, the venule blood flow is a kermesinus grain linear flow, after the administration, NS group blood flow, blood vessel directly do not have significant change, and grieved liquid group and TONGSAIMAI group arteriole blood flow are the cerise linear flow, the venule blood flow is dark red colo(u)r streak grain stream, arteriole and venule caliber all enlarge markedly, and have a net increase of depreciation and NS group behind its medicine and carry out the same period relatively, the results are shown in Table 11, table 12 and photo (adnexa 1).
The grieved liquid of table 11 influences net added value behind the group n dosage medicine prodrug (um, X ± SD) to the arteriole caliber
(g/kg) (um, 10min 20min 40minNS 10 17.20 ± 5.97 0.98 ± 1.99 0.87 ± 2.07 0.41 ± 2.90 TONGSAIMAI liquid 10 10 18.74 ± 7.04 of X ± SD)
*6.04 ± 6.02
*8.16 ± 3.37
* *9.01 ± 8.56
* *Grieved liquid 10 20 15.92 ± 3.74
*8.47 ± 3.88
* *9.44 ± 5.51
* *10.58 ± 6.00
* *
10 10 15.92±1.99
* 7.05±5.91
** 7.73±3.96
***?6.06±5.11
**
With NS group ratio,
*P＞0.05,
*P＜0.05,
* *P＜0.01
The grieved liquid of table 12 influences net added value behind the group n dosage medicine prodrug (um, X ± SD) to the venule caliber
(g/kg) (um, 10min 20min 40minNS 10 39.72 ± 12.05 4.09 ± 4.54 2.40 ± 2.10 0.98 ± 2.56 TONGSAIMAI liquid 10 10 35.32 ± 11.24 of X ± SD)
*10.18 ± 4.93
*11.02 ± 5.97
* *10.12 ± 5.90
* *Grieved liquid 10 20 40.16 ± 13.88
*11.80 ± 9.66
*11.96 ± 8.53
* *11.84 ± 9.51
* *
10 10 40.16±8.80
* 8.29±4.22
** 13.08±10.44
**?9.13±6.51
***
With NS group ratio,
*P＞0.05,
*P＜0.05,
* *P＜0.01
By table 11, table 12 as seen, grieved liquid is oral, and Mice Auricle arteriole, venule caliber enlarge markedly, and proves this product energy microcirculation improvement, accelerates blood flow.
3.3.8 hematoma model test: 75 of male mices, 24-28g is divided into 5 groups at random.3 administration groups are distinguished the grieved liquid 5g/kg of ig, 10g/kg, 20g/kg, blank group ig isometric(al) normal saline, positive controls ig Radix Notoginseng liquid 3g/kg, continuous 7 days.Imitative literature method is done the ecchymosis moulding before the administration
[11]: every Mus one branch hole rear vein beard is got blood 0.5ml, adds the 0.1MCaCl that contains penicillin 100,000 units
2Solution 0.1ml mixing, it is subcutaneous to inject self nape portion immediately, causes ecchymosis.By last method administration 7 days, put to death in 8th after the moulding, separate the ecchymosis enclosed mass, scales/electronic balance weighing.The results are shown in Table 13.
Table 13 pair mice ecchymosis influence group n dosage (the clot weight of g/kg * d) (mg, NS 15 33.7 ± 20.3 Radix Notoginseng liquid 15 3 * 7 17.3 ± 12.5 of X ± SD)
*Grieved liquid 15 20 * 7 18.8 ± 13.8
*
15 10×7 19.9±16.1
**
15 5×7 22.1±14.0
*
With NS group ratio,
*P＞0.05,
*P＜0.05
By table 13 as seen, grieved liquid is oral, and the clot weight of mice self ecchymosis significantly alleviates, and illustrates that this product can promote absorption of hematoma, has the effect of eliminating blood stasis.Above-mentioned 3.3.1-3.3.8 is totally 8 tests, shows that grieved liquid can prolong clotting time, thrombin time, blood plasma recalcification time, blood viscosity lowering, suppress thrombosis, blood vessel dilating, microcirculation improvement, promote absorption of hematoma, prove that from different perspectives this product has significant blood circulation invigorating efficacies.
3.4 dampen the model therapeutic test: 60 of male rats, 250-300g is divided into 4 groups at random.Reference literature
[12]Method is made the acute soft tissue injury model: moulding is preceding with 1%Na
2S solution removes the big leg outer side hair in back, raises 3, hits the depilation position continuously 3 times with making the potential energy of beating device with 0.2kg * 0.5m by oneself, causes the acute contusion of local soft tissue.Damage and began administration the same day, 2 the grieved liquid 10g/kg of administration group difference ig, 20g/kg, blank group ig isometric(al) normal saline, positive controls ig Radix Notoginseng liquid 3g/kg.Administration every day 1 time, and do following observation.
Observation index and result
(1) damage disease index.Press finding of naked eye swelling, ecchymosis, dyskinetic degree weight rank scores, 1,3,6 records respectively after administration.Drafting standards of grading is:
Damage disease index standards of grading
The classification of disease degree weight
Not obvious limb swelling 012 local ecchymosis 012 dyskinesia 012 of obviously seriously hindering
The results are shown in Table 14.
Therapeutic effect group dosage (g/kg) the damage disease index that table 14 pair rat hindlimb is dampened (X ± SD)
d
1(n) d
3(n) d
6(n) NS 5.5 ± 0.5 (12) 3.2 ± 0.4 (9) 2.0 ± 0.1 (6) Radix Notoginseng liquid 3 5.5 ± 0.7
*(12) 1.8 ± 0.4
* *(9) 0.7 ± 0.8
* m2(6) grieved liquid 20 5.8 ± 0.4
*(12) 1.7 ± 0.5
* *(9) 0.3 ± 0.5
* *(6)
10 5.2±0.4
*(12) 2.2±0.4
***(9) 0.6±0.9
**(6)
With NS group ratio,
*P＞0.05,
*P＜0.05,
* *P＜0.01
By table 14 as seen, rat is taken grieved liquid, dampens rapidly and repairs, and the disease index significantly is lower than the normal saline matched group, shows that this product has therapeutic effect to acute soft tissue injury.
(2) histopathologic examination.12h, 24h, 3d, 6d after the administration cut the pars affecta specimen, and 3 every group, formalin fixed is sent the pathological tissue inspection.Microscopy is seen, and damage location has changes such as edema, hemorrhage, cell infiltration, connective tissue proliferation.Each organizes the basic pathology similar process, but the degree difference: hemorrhage between the subcutaneous and flesh of damage early stage (12h, 24h after the administration), the blank group is serious, and each administration is given lighter; Damage later stage (3d, 6d after the administration) connective tissue proliferation, the blank group is obvious, each administration group not obvious (referring to the report of adnexa 2,3 histopathologic examinations, photo).
This shows that it is hemorrhage to alleviate damage location, suppress connective tissue proliferation, relevant with the mechanism that grieved liquid treatment is dampened.
4, conclusion (of pressure testing): this paper tests and obtains following result: (1) grieved liquid makes mice antimony potassium tartrate writhing response significant prolongation incubation period, turns round the body number of times and significantly reduces.(2) make the mice electricity irritation cause pain significant prolongation incubation period.(3) alleviate rat paw edema due to the carrageenin.(4) alleviate Oleum Tiglii induced mice auricle edema.(5) prolong clotting time of mice, thrombin time, blood plasma recalcification time.(6) reduce the rat whole blood viscosity.(7) suppressing rat moves-vein bypass thrombosis.(8) expansion rat hindlimb blood vessel increases perfusion flow.(9) expansion Mice Auricle arteriole, venule, microcirculation improvement.(10) promote the mice ecchymosis to absorb, alleviate clot weight.(11) rat hindlimb acute soft tissue injury model there is therapeutic effect, damage disease index is reduced, alleviate hemorrhagely, suppress connective tissue proliferation.The above results shows that Capsule for treating wound has the effect of good analgesia, antiinflammatory, blood circulation promoting and blood stasis dispelling and reparation damage, is applicable to the disease based on stagnation of blood stasis such as soft tissue injury, vasculitis.2 composite preparation toxicological studies of experimental example
Acute toxicity test in mice gavages with Capsule for treating wound water extract, can not measure LD
50The maximum dosage-feeding test, mice ig80g (being equivalent to the medical material amount)/kg (for 240 times of clinical consumptions) does not occur dead, the body weight normal growth.
The rat long term toxicity test, high dose group ig40g/kg (being 125 times of clinical consumptions), medication 90 days (be clinical course of treatment 9 times), all not dead, the body weight normal growth, through blood test, serum biochemistry check, main organs coefficient determination and histopathology check, there is no the overt toxicity reaction.Experimental example 3 clinical test results
According to State Administration of Traditional Chinese Medicine " disease of tcm diagnosis criterion of therapeutical effect ", selecting acute thoracic side of body bruise is clinical disease, carry out clinical observation research, and do contrast with notoginseng vulnerary capsule (authentication code 96 is defended the accurate word Z-101 of medicine number) and observe, do the evaluation of safety and clinical efficacy.Clinical trial divides II, two stages of III phase to finish.
The II clinical trial phase is many bases clinical trial of randomized, double-blind, positive drug parallel control.Test is undertaken at random by the base layer and section.Medicine is packed A, B medicine in the medicated bag into by the random table requirement, and 1-60 medicine numbering dispense medicament is pressed at every center.After research is finished, the blind end of contrast center design, disclose A, B, hand over statistical analysis, after all statistics is finished, disclose investigational agent and respectively contrast medicine.The II clinical trial phase is the result show: Capsule for treating wound total effective rate 95%, cure-remarkable-effectiveness rate 86%; And notoginseng vulnerary capsule total effective rate 82%, cure-remarkable-effectiveness rate 67%.
The III clinical trial phase adopts many bases method of open trial at random.Finish test group 300 examples, matched group 100 routine patient's clinical trials are estimated, and by random table medicine numbering 1-100 are set, and each test center is provided medicine by numbering.The III clinical trial phase is the result show: the total effective rate 96% of Capsule for treating wound, cure-remarkable-effectiveness rate 90.3%; Contrast medicine notoginseng vulnerary capsule total effective rate 84%, cure-remarkable-effectiveness rate is 70%.Capsule for treating wound is aspect acute thoracic side of body bruise, and total effects obviously is better than the notoginseng vulnerary capsule, and in its process of the test, 600 routine patients do not see any untoward reaction.Experimental example 4 preparation process are preferably studied
1, temperature: with water is solvent, and extracting temperature is 100 ℃, needn't investigate.
2, to the investigation of amount of water, decocting time, decoction number of times: to above three, by three factors, three levels are index with orthogonal design arrangement test with the content of emodin in dry extract, find out the optimum process condition of each factor, wherein factor and level arrangement see Table 15.
Table 15 experimental factor and level
Factor
Water
Add water multiple decocting time (h) and decoct number of times
Flat
A B C
1 8 0.5 1
2 2 0.75 2
3 15 1.0 3 concrete experimental techniques:
Ratio in each medical material in the prescription takes by weighing, and taking by weighing total amount is totally 9 parts of 100g, soaks half an hour respectively, decocts, and filters, concentrate, and vacuum drying, dried cream porphyrize is crossed 65 mesh sieves, gets totally 9 parts of extract dry powder.Every part is extracted 8 hours to extracting liquid colourless with the methanol Soxhlet respectively, reclaims methanol to doing, and adding distil water is an amount of, transfers PH2～3 with HCl, hydrolysis 2 hours, and extracted with diethyl ether 8 times, combined ether liquid reclaims ether to doing, and the dehydrated alcohol standardize solution is in the 10ml volumetric flask.
Putting each sample liquid 5 μ l of above-mentioned preparation respectively on 200 * 100 * 0.4mm silica gel plate, compare with the emodin reference substance, be developing solvent with benzene-ethyl acetate-formic acid (30: 10: 1), launches, and taking-up is dried, on CS-9000 type thin-layer chromatogram scanner at λ
s=420nm, λ
RThe peak area value of working sample under the=550nm condition.
Try to achieve in the orthogonal table emodin content in 9 groups of experiments by above detection and calculating, carry out simultaneously that quadrature analysis and The results of analysis of variance see Table 16, table 17.
Table 16 L
9(3)
4Orthogonal experiments
The quadrature analysis of sample peak dot sample amount emodin group level and factor
Area (Yi) (μ l) content (mg) 1 9555.173
*5 2.1328 k
111.5593 14.7504 12.72802 19584.870 5 4.4635 k
214.5375 15.8214 16.62613 21734.367 5 4.9630 k
321.1368 16.6618 17.87954 21466.702 5 4.9008 A3 B3 C35,22752.958 5 5.1997 k
13.8531 4.9168 4.24276 19470.832 5 4.4370 k
24.8458 5.2738 5.54207 33584.789 5 7.7168 k
37.0456 5.5539 5.95988 26877.669 5 6.1582 R, 3.1925 0.6371 1.71719 31626.788 5 7.2618 A＞B＞C
Table 17 L
9(3)
4Analysis of variance table
The mean square F P of source of variation sum of sguares of deviation from mean degree of freedom
A factor 16.02 2 8.010 22.25＜0.05
B factor 0.61 2 0.305 0.847＞0.05
C factor 4.81 2 2.405 6.681＞0.05
Error 0.72 2 0.360
Amount to 22.16 8
Conclusion: three factors are A＞B＞C (promptly adding water multiple＞decoction number of times＞decocting time) in proper order to the influence of this experiment.The optimum condition of each level is: A
3, B
3, C
3(promptly add 15 times of amounts of water, decocting time 1hr, decoct 3 times).Variance analysis thinks that the A factor has the significance influence to experimental result, and the level of B, C two factors is not obvious to the experimental result influence.
According to above situation, in conjunction with save time, energy consumption and real work custom, we choose and have used B
2And C
2Comprehensively above-mentioned, each level of this orthogonal experiment is defined as A
3B
2C
2
Checking: owing to do not have the experiment of this group in the orthogonal table, therefore by the condition A that optimizes
3B
2C
2Repeat above-mentioned experiment, concrete grammar is the same, get 2 parts of the medical material amounts of the same experiment, experimentation slightly, testing result is as follows: emodin content is respectively: 7.4609 (mg), 7.6371 (mg), average: 7.5490 (mg), with the highest group of basically identical of the 7th group of emodin content in the orthogonal experiment, zero difference on the statistics.
3, the medical material granularity is investigated
Get 6 parts of former side 100g medical materials, 1 part breaks into fine grained (Semen phaseoli radiati is big, n=2), 1 part breaks into coarse granule (Semen Persicae is big, and n=2), another part is not processed, with the pharmaceutical decocting piece of buying (n=2), add 15 times of water gagings respectively, soaked 0.5 hour, decoct secondary, each 0.75 hour, filtrate is concentrated, and precipitate with ethanol (containing alcohol amount 30%) reclaims alcohol, concentrated, dry.Get extract dry powder, weigh.Calculate the percentage rate that extracts extractum.
Thin layer is measured, and calculates the percentage composition of emodin, the results are shown in Table 18:
Table 18 medical material granularity is investigated project medical material fine grained medical material coarse granule pharmaceutical decocting piece emodin content (mg) 2.03 1.93 1.72 extract dry powder yield % (g/g) 15.01 (n=2) 14.7 (n=2) 13.47 (n=2) as a result
By The above results as can be seen medical material fine grained extractum and emodin content mostly be 15.01 and 2.03 most, but when experiment decocts inconvenient operation, and easily burnt, bonding is so but become coarse granule as the conditions permit powder.
4, medical material soaks and investigates: get 6 parts of former side 100g medical materials, 1 part is not soaked (n=2), and 1 part is soaked 0.5 hour (n=2), and 1 part is soaked 1 hour (n=2) in addition, and the same extract dry powder that is prepared into is weighed, and asks percentage rate.Precision takes by weighing extract dry powder 5.0g, extracts operation by 2 experimental technique items from 120ml methanol Soxhlet, and preparation is for test agent liquid, point sample, launches, dries, and thin layer is measured, and calculates the percentage composition of emodin, the results are shown in Table 19:
The immersion of table 19 medical material is investigated as a result, and the project medical material does not soak 1 hour emodin content (mg) 1.54 1.76 1.82 yield of extract % (g/g) 12.1 13.4 13.7 of medical material immersion medical material immersion in 0.5 hour
Above result sees that medical material soaks 1 hour emodin content height, secondly for soaking 0.5 hour and not soaking.Consider to soak and to be more or less the same with 0.5 hour in 1 hour, for saving man-hour, so medical material is selected to soak 0.5 hour.
5, the selection of alcohol precipitation concentration: this preparation process reduces dosage, therefore the design deimpurity technology of ethanol precipitation guaranteeing to reduce the proposition of impurity as much as possible under the constant substantially prerequisite of former side's drug effect and active ingredient.The effect experiment method: be index incubation period to this product with causing bitterly with clotting time.The anticoagulant test is adopted capillary tube method to make clotting time of mice and is measured, and blank group (ig NS) clotting time is 82.6 ± 14.1S.The mice heat test is adopted in the analgesic test, and be 18.6 ± 6.1S the pain incubation period of causing of blank group.Find out by last result, add a certain amount of ethanol precipitation impurity, pharmacological action is strengthened relatively, yield of extract significantly reduces, and active constituent content, improve increase to some extent with alcohol precipitation concentration, and 30% concentration group and 40% concentration group emodin content are higher than not carrying out precipitate with ethanol behind the precipitate with ethanol, may be because the precipitate with ethanol experiment be to use same decoction liquor, be divided into four parts, do 10%, 20%, 30%, 40% precipitate with ethanol relatively, detect emodin content, and the sample that does not add precipitate with ethanol is not with a collection of, and is perhaps slightly variant.Comprehensive precipitate with ethanol is tested every result.Select that to contain 30% alcohol precipitation aggregative indicator better for use, pharmacological action is strong.
6, excipient is selected: because the easy moisture absorption of Chinese medical concrete, put caking for a long time, need select suitable hygroscopic agent for use, according to document and preliminary test, following hygroscopic agent is investigated, and the capsule that will make of different excipient was placed 1 month in the calorstat that temperature is 25 ± 0.1 ℃ in humidity 60%, observe capsule 's content and have or not the deliquescence phenomenon, the results are shown in Table 20.
Table 20 excipient selection result
Dextrin starch calcium sulfate calcium hydrogen phosphate calcium hydrogen phosphate+starch consumption % 52524242 (6+2) (4+2) (g/g) deliquescence degree-+-+-+-+---annotate: the medicated cap end has slight caking in the+capsule 's content
-capsule 's content has the slight moisture absorption, and is mobile fair
--capsule 's content no change, good hand touch
See that by above result one group of calcium hydrogen phosphate+starch (6+2) is effective, this preparation is selected this group excipient for use.
7, granulation is selected with concentration of alcohol
This is granulated and selects ethanol is solvent, takes by weighing a certain amount of extract dry powder, granulates with different concentration ethanol, the results are shown in Table 21:
Table 21 different concentration ethanol granulation result
75% ethanol, 80% ethanol, 85% ethanol, 90% alcohol 95 % ethanol
Forming the agglomerating shape of bulk becomes block bonding bonding more open
Fruit can't be granulated that can't granulate to granulate and can't granulate and is graininess by screen cloth smoothly
By above result, select 95% alcohol granulation for use.
Following embodiment all can realize the effect of above-mentioned experimental example.
Embodiment 1:Capsule
Radix Et Rhizoma Rhei 380g Radix Angelicae Sinensis 304g Radix Bupleuri 304g Radix Trichosanthis 304g
Semen Persicae (peeling) 227g Flos Carthami 227g vinegar Rhizoma Corydalis 227g Radix Glycyrrhizae 150g,
More than eight flavors, add 15 times of water gagings and soak and decoct 2 times, each 45 minutes, collecting decoction, filter, filtrate is concentrated into 20 ℃ of relative densities 1.017～1.038, adds ethanol and makes and contain the alcohol amount and reach 30%, left standstill 12 hours, and filtered filtrate recycling ethanol, be concentrated into the extractum shape, drying adds calcium hydrogen phosphate 18g, starch 6g, mixing is made granule, incapsulate, make 1000, promptly.Effect: blood circulation promoting and blood stasis dispelling, promoting the circulation of QI to relieve pain.Cure mainly: traumatic injury, pain in chest and hypochondrium belongs to the stagnation of QI and blood person.Usage: every day 3 times, at every turn obey 3.Serveing on 10 days was 1 course of treatment.
Embodiment 2:Oral liquid
Radix Et Rhizoma Rhei 370g Radix Angelicae Sinensis 294g Radix Bupleuri 294g Radix Trichosanthis 314g
Semen Persicae (peeling) 240g Flos Carthami 240g vinegar Rhizoma Corydalis 210g Radix Glycyrrhizae 160g,
More than eight flavors, add 16 times of water gagings and soak and decoct 2 times, each 40 minutes, collecting decoction filtered, filtrate is concentrated into 20 ℃ of relative densities 1.017～1.038, adds ethanol and makes and contain alcohol amount and reach 35%, leaves standstill 13 hours, filters, filtrate recycling ethanol, water liquid adds water to 1000ml with sucrose 150g, promptly.Usage: every day 3 times, at every turn obey 10ml.Serveing on 10 days was 1 course of treatment.
Embodiment 3: granule
Radix Et Rhizoma Rhei 390g Radix Angelicae Sinensis 314g Radix Bupleuri 314g Radix Trichosanthis 294g
Semen Persicae (peeling) 217g Flos Carthami 217g vinegar Rhizoma Corydalis 217g Radix Glycyrrhizae 140g,
More than eight flavors, add 16 times of water gagings and soak and decoct each 40 minutes 2 times, collecting decoction filters, and filtrate is concentrated into 20 ℃ of relative densities 1.017～1.038, add ethanol and make and contain alcohol amount and reach 35%, left standstill 13 hours, filter, filtrate recycling ethanol, be concentrated into the extractum shape, dextrin is made granule in right amount, makes 1000g, promptly get 200 bags, every bag of 5g.Usage: every day 3 times, at every turn obey 1 bag.Serveing on 10 days was 1 course of treatment.The method of quality control of embodiment 4 capsules is differentiated: a. gets this product content 2g, adds methanol 30ml supersound process 15 minutes, filters, and filtrate is concentrated into about 2ml, as need testing solution.Other gets Radix Et Rhizoma Rhei control medicinal material 1g, gets control medicinal material solution with legal system.Get the emodin reference substance again, add methanol and make the solution that contains 0.1mg among every 1ml, in contrast product solution.According to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B) test, draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with 30: 10: 1 benzene-ethyl acetate-formic acid was developing solvent, launched, and took out, dry, put under the 365nm ultra-violet lamp and inspect.In the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color respectively.B. get this product content 4g, add methanol 40ml, supersound process 20 minutes, filter, filtrate evaporate to dryness, residue add water 20ml makes dissolving, add dilute hydrochloric acid and transfer about pH value to 2, use ether extraction 3 times, each 20ml, 15ml, 15ml merges ether extracted liquid, extract 3 times each 20ml, 10ml with 2% sodium carbonate liquor, 10ml divides the water intaking layer, with ethyl acetate 15ml washing, discard the ethyl acetate washing liquid, transfer pH value to 2～3, with benzene 15ml washing with salt, discard benzene liquid, continue and use ether extraction 3 times, each 20ml, 15ml, 15ml, ether extracted liquid evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution.Other gets the ferulic acid reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography solution (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B), draw need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 30: 10: 1 benzene-ethyl acetate-formic acid was developing solvent, launched, and took out, dry, put under the 365nm ultra-violet lamp and inspect.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical navy blue fluorescence speckle.C. get this product content 4g, add methanol 30ml supersound process 15 minutes, filter the filtrate evaporate to dryness, residue adds water 20ml makes dissolving, and enriching ammonia number droplet is transferred more than the pH value to 9, and with ether extraction 2 times, each 20ml merges ether solution, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 1mg among every 1ml, in contrast product solution, test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B), draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with 7.5: 4: 1 normal hexane-chloroform-methanols was developing solvent, launch, take out, dry, put smoke in the iodine steam after, put under the 365nm ultra-violet lamp and inspect.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.Assay: get this product content 2g, the accurate title, decide, put in the apparatus,Soxhlet's, it is an amount of to add methanol, heating and refluxing extraction, to extracting liquid colourless, extracting solution reclaims methanol to doing, and residue adds water 50ml, transfers pH value to 2～3 with rare HCl, put in the 90-95 ℃ of water-bath hydrolysis 2 hours, hydrolyzed solution quantitatively is transferred in the separatory funnel, adds diethyl ether to extract 8 times, each 50ml, merge extractive liquid,, reclaim ether to doing, residue adds dehydrated alcohol and quantitatively is transferred in the 5ml volumetric flask, adds dehydrated alcohol to scale, shake up, as need testing solution.Other gets the emodin reference substance, adds dehydrated alcohol and makes the solution that contains 0.1mg among every 1ml, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B), draw need testing solution 5 μ l, reference substance solution 2 μ l and 4 μ l, put respectively on same silica gel g thin-layer plate, with 30: 10: 1 benzene-ethyl acetate-formic acid was developing solvent, launched, and took out, dry, carry out scanning wavelength λ according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia nineteen ninety-five version B thin layer chromatography scanning)
s=420nm, λ
R=550nm measures test sample trap integrated value and reference substance trap integrated value, calculates, promptly.Every of this product contains Radix Et Rhizoma Rhei by emodin (C
15H
10O
5) meter, must not be less than 0.034mg.
Claims (11)
1, a kind of treatment traumatic injury, the Chinese medicine compositions of pain in chest and hypochondrium is characterized in that this pharmaceutical composition made by following raw material medicaments:
Radix Et Rhizoma Rhei 360-400 weight portion Radix Angelicae Sinensis 280-320 weight portion
Radix Bupleuri 280-320 weight portion Radix Trichosanthis 280-320 weight portion
Semen Persicae 200-250 weight portion Flos Carthami 200-250 weight portion
Rhizoma Corydalis 200-250 weight portion Radix Glycyrrhizae 130-170 weight portion.
2, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw material medicaments:
Radix Et Rhizoma Rhei 380 weight portion Radix Angelicae Sinensis 304 weight portion Radix Bupleuri 304 weight portions
Radix Trichosanthis 304 weight portion Semen Persicaes 227 weight portion Flos Carthamis 227 weight portions
Rhizoma Corydalis 227 weight portion Radix Glycyrrhizaes 150 weight portions.
3,, it is characterized in that the preferred Semen Persicae (peeled) of Semen Persicae described in this pharmaceutical composition, the preferred vinegar Rhizoma Corydalis of Rhizoma Corydalis as claim 1,2 described pharmaceutical compositions.
4, preparation of drug combination method as claimed in claim 3, it is characterized in that this method is: above eight flavors, add 13-17 times of water gaging and soak decoction 1-3 time, each 35-55 minute, collecting decoction, filter, filtrate is concentrated into 15-25 ℃ of relative density 1.00～1.05, adds ethanol and makes and contain alcohol amount and reach 25-35%, leaves standstill 10-14 hour, filter, filtrate recycling ethanol is concentrated into the extractum shape, drying, through conventional operation directly or add pharmaceutically acceptable excipient and make clinical acceptable forms, as tablet, oral liquid, capsule, granule.
5, preparation of drug combination method as claimed in claim 4 is characterized in that the preparation method of capsule is: above eight flavors add 15 times of water gagings and soak decoction 2 times, each 45 minutes, collecting decoction filters, and filtrate is concentrated into 20 ℃ of relative densities 1.017～1.038, add ethanol and make and contain alcohol amount and reach 30%, left standstill 12 hours, filter, filtrate recycling ethanol is concentrated into the extractum shape, drying, add calcium hydrogen phosphate 18g, starch 6g, mixing, make granule, incapsulate, promptly.
6, require the method for quality control of 3 described drug combination preparations as profit, it is characterized in that discrimination method in this method comprises one or more in the following discriminating: a. gets this composite preparation 2g, add methanol 30ml supersound process 10-20 minute, filter, filtrate is concentrated into about 2ml, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 1g, gets control medicinal material solution with legal system; Get the emodin reference substance again, add methanol and make the solution that contains 0.1mg among every 1ml, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color respectively; B. get this composite preparation 4g, add methanol 40ml, supersound process 15-25 minute, filter, the filtrate evaporate to dryness, residue adds water 20ml makes dissolving, adds dilute hydrochloric acid and transfers about pH value to 2, uses ether extraction 3 times, merge ether extracted liquid, extract 3 times with 2% sodium carbonate liquor, divide the water intaking layer, with ethyl acetate 15ml washing, discard the ethyl acetate washing liquid, transfer pH value to 2～3 with salt,, discard benzene liquid with benzene 15ml washing, continue and use ether extraction 3 times, ether extracted liquid evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography solution trial, draw need testing solution 10 μ l, reference substance solution 5 μ l put respectively on same silica gel g thin-layer plate, and with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical navy blue fluorescence speckle; C. get this composite preparation 4g, add methanol 30ml supersound process 10-20 minute, filter, filtrate evaporate to dryness, residue add water 20ml makes dissolving, enriching ammonia number droplet is transferred more than the pH value to 9, with ether extraction 1-3 time, each 20ml merges ether solution, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 1mg among every 1ml, in contrast product solution, test according to thin layer chromatography, draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with 6-8.5: 3-5: 1-2 normal hexane-chloroform-methanol is developing solvent, launch, take out, dry, put smoke in the iodine steam after, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
7, require the method for quality control of 6 described drug combination preparations as profit, the discrimination method that it is characterized in that capsule comprises one or more in the following discriminating: a. gets this product content 2g, add methanol 30ml supersound process 15 minutes, filter, filtrate is concentrated into about 2ml, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 1g, gets control medicinal material solution with legal system; Get the emodin reference substance again, add methanol and make the solution that contains 0.1mg among every 1ml, in contrast product solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with 30: 10: 1 benzene-ethyl acetate-formic acid, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color respectively; B. get this product content 4g, add methanol 40ml, supersound process 20 minutes, filter, filtrate evaporate to dryness, residue add water 20ml makes dissolving, add dilute hydrochloric acid and transfer about pH value to 2, use ether extraction 3 times, each 20ml, 15ml, 15ml merges ether extracted liquid, extract 3 times each 20ml, 10ml with 2% sodium carbonate liquor, 10ml divides the water intaking layer, with ethyl acetate 15ml washing, discard the ethyl acetate washing liquid, transfer pH value to 2～3, with benzene 15ml washing with salt, discard benzene liquid, continue and use ether extraction 3 times, each 20ml, 15ml, 15ml, ether extracted liquid evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography solution trial, draw need testing solution 10 μ l, reference substance solution 5 μ l put respectively on same silica gel g thin-layer plate, are developing solvent with 30: 10: 1 benzene-ethyl acetate-formic acid, launch, and take out, and dry, and put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical navy blue fluorescence speckle; C. get this product content 4g, add methanol 30ml supersound process 15 minutes, filter the filtrate evaporate to dryness, residue adds water 20ml makes dissolving, and enriching ammonia number droplet is transferred more than the pH value to 9, and with ether extraction 2 times, each 20ml merges ether solution, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 1mg among every 1ml, in contrast product solution, test according to thin layer chromatography, draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with 7.5: 4: 1 normal hexane-chloroform-methanols was developing solvent, launch, take out, dry, put smoke in the iodine steam after, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
8, require the method for quality control of 3 described drug combination preparations as profit, it is characterized in that the content assaying method in this method is: get this composite preparation 2g, the accurate title, decide, and puts in the apparatus,Soxhlet's, it is an amount of to add methanol, heating and refluxing extraction, to extracting liquid colourless, extracting solution reclaims methanol to doing, residue adds water 50ml, transfer pH value to 2～3.5 with rare HCl, put in the 85-95 ℃ of water-bath hydrolysis 1-3 hour, hydrolyzed solution quantitatively is transferred in the separatory funnel, add diethyl ether and extract 7-9 time, each 50ml, merge extractive liquid, reclaims ether to doing, residue adds dehydrated alcohol and quantitatively is transferred in the 5ml volumetric flask, add dehydrated alcohol to scale, shake up, as need testing solution; Other gets the emodin reference substance, adds dehydrated alcohol and makes the solution that contains 0.1mg among every 1ml, in contrast product solution; According to the thin layer chromatography test, draw need testing solution 5 μ l, reference substance solution 2 μ l and 4 μ l, put respectively on same silica gel g thin-layer plate, with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, take out, dry, carry out scanning wavelength λ according to thin layer chromatography
s=420nm, λ
R=550nm measures test sample trap integrated value and reference substance trap integrated value, calculates, promptly; This composite preparation per unit amount contains Radix Et Rhizoma Rhei by emodin, must not be less than 0.030-0.038mg.
9, require the method for quality control of 8 described pharmaceutical preparatioies as profit, the content assaying method that it is characterized in that capsule is: get this product content 2g, the accurate title, decide, and puts in the apparatus,Soxhlet's, it is an amount of to add methanol, heating and refluxing extraction, to extracting liquid colourless, extracting solution reclaims methanol to doing, residue adds water 50ml, transfer pH value to 2～3 with rare HCl, put in the 90-95 ℃ of water-bath hydrolysis 2 hours, hydrolyzed solution quantitatively is transferred in the separatory funnel, add diethyl ether and extract 8 times, each 50ml, merge extractive liquid, reclaims ether to doing, residue adds dehydrated alcohol and quantitatively is transferred in the 5ml volumetric flask, add dehydrated alcohol to scale, shake up, as need testing solution; Other gets the emodin reference substance, adds dehydrated alcohol and makes the solution that contains 0.1mg among every 1ml, in contrast product solution; According to the thin layer chromatography test, draw need testing solution 5 μ l, reference substance solution 2 μ l and 4 μ l, putting respectively on same silica gel g thin-layer plate, is developing solvent with 30: 10: 1 benzene-ethyl acetate-formic acid, launches, take out, dry, carry out scanning wavelength λ according to thin layer chromatography
s=420nm, λ
R=550nm measures test sample trap integrated value and reference substance trap integrated value, calculates, promptly; Every of this product contains Radix Et Rhizoma Rhei by emodin, must not be less than 0.034mg.
10, the method for quality control of drug combination preparation as claimed in claim 3, it is characterized in that this method may further comprise the steps: differentiate: a. gets this composite preparation 2g, adds methanol 30ml supersound process 10-20 minute, filters, filtrate is concentrated into about 2ml, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 1g, gets control medicinal material solution with legal system; Get the emodin reference substance again, add methanol and make the solution that contains 0.1mg among every 1ml, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color respectively; B. get this composite preparation 4g, add methanol 40ml, supersound process 15-25 minute, filter, the filtrate evaporate to dryness, residue adds water 20ml makes dissolving, adds dilute hydrochloric acid and transfers about pH value to 2, uses ether extraction 3 times, merge ether extracted liquid, extract 3 times with 2% sodium carbonate liquor, divide the water intaking layer, with ethyl acetate 15ml washing, discard the ethyl acetate washing liquid, transfer pH value to 2～3 with salt,, discard benzene liquid with benzene 15ml washing, continue and use ether extraction 3 times, ether extracted liquid evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography solution trial, draw need testing solution 10 μ l, reference substance solution 5 μ l put respectively on same silica gel g thin-layer plate, and with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, and takes out, and dries, and puts under the ultra-violet lamp and inspects; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical navy blue fluorescence speckle; C. get this composite preparation 4g, add methanol 30ml supersound process 10-20 minute, filter, filtrate evaporate to dryness, residue add water 20ml makes dissolving, enriching ammonia number droplet is transferred more than the pH value to 9, with ether extraction 1-3 time, each 20ml merges ether solution, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 1mg among every 1ml, in contrast product solution, test according to thin layer chromatography, draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with 6-8.5: 3-5: 1-2 normal hexane-chloroform-methanol is developing solvent, launch, take out, dry, put smoke in the iodine steam after, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; Assay: get this composite preparation 2g, the accurate title, decide, put in the apparatus,Soxhlet's, it is an amount of to add methanol, heating and refluxing extraction, to extracting liquid colourless, extracting solution reclaims methanol to doing, and residue adds water 50ml, transfers pH value to 2～3.5 with rare HCl, put in the 85-95 ℃ of water-bath hydrolysis 1-3 hour, hydrolyzed solution quantitatively is transferred in the separatory funnel, adds diethyl ether to extract 7-9 time, each 50ml, merge extractive liquid,, reclaim ether to doing, residue adds dehydrated alcohol and quantitatively is transferred in the 5ml volumetric flask, adds dehydrated alcohol to scale, shake up, as need testing solution; Other gets the emodin reference substance, adds dehydrated alcohol and makes the solution that contains 0.1mg among every 1ml, in contrast product solution; According to the thin layer chromatography test, draw need testing solution 5 μ l, reference substance solution 2 μ l and 4 μ l, put respectively on same silica gel g thin-layer plate, with 25-35: 8-12: 1-2 benzene-ethyl acetate-formic acid is developing solvent, launches, take out, dry, carry out scanning wavelength λ according to thin layer chromatography
s=420nm, λ
R=550nm measures test sample trap integrated value and reference substance trap integrated value, calculates, promptly; This composite preparation per unit amount contains Radix Et Rhizoma Rhei by emodin, must not be less than 0.030-0.038mg.
11, Chinese medicine composition as claimed in claim 3 is in preparation treatment traumatic injury, the application in the pain in chest and hypochondrium medicine.
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| CN 03131143 CN1267117C (en) | 2003-05-14 | 2003-05-14 | A Chinese medicinal composition for treating traumatic injury and pain in chest and hypochondrium, and its preparation method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102697903A (en) * | 2012-05-11 | 2012-10-03 | 贾晋科 | Medicine for treating herpes zoster |
| CN102861197A (en) * | 2012-10-24 | 2013-01-09 | 王雨 | Traditional Chinese medicine composition for treating injuries from falls, fractures, contusions and strains |
| CN103293269A (en) * | 2012-03-02 | 2013-09-11 | 迪沙药业集团有限公司 | Quality control method of Chinese medicine composition for treating vascular dementia |
| CN103536681A (en) * | 2013-10-25 | 2014-01-29 | 李直韩 | Fracture-setting traditional Chinese medicine composition as well as preparation process thereof |
-
2003
- 2003-05-14 CN CN 03131143 patent/CN1267117C/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103293269A (en) * | 2012-03-02 | 2013-09-11 | 迪沙药业集团有限公司 | Quality control method of Chinese medicine composition for treating vascular dementia |
| CN102697903A (en) * | 2012-05-11 | 2012-10-03 | 贾晋科 | Medicine for treating herpes zoster |
| CN102861197A (en) * | 2012-10-24 | 2013-01-09 | 王雨 | Traditional Chinese medicine composition for treating injuries from falls, fractures, contusions and strains |
| CN103536681A (en) * | 2013-10-25 | 2014-01-29 | 李直韩 | Fracture-setting traditional Chinese medicine composition as well as preparation process thereof |
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| Publication number | Publication date |
|---|---|
| CN1267117C (en) | 2006-08-02 |
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Application publication date: 20031126 Assignee: YANGLING CHARISMA BIO-PHARMACEUTICAL Co.,Ltd. Assignor: Yu Hui Contract record no.: 2019990000184 Denomination of invention: Chinese medicine composition for curing traumatic injury and pains in chest and hypochondrium and its preparing method Granted publication date: 20060802 License type: Exclusive License Record date: 20190603 |
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