CN1256940C - Compound Chinese medicine notoginseng dripping pills and its prepn process - Google Patents
Compound Chinese medicine notoginseng dripping pills and its prepn process Download PDFInfo
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Abstract
The present invention relates to a compound Chinese medicine notoginseng dripping pill in oral administration and a preparation method thereof. The compound notoginseng dripping pill of the present invention is a medicament prepared by radix notoginseng, astragalus roots, red sage roots, scrophularia roots and polyethylene glycol 4000 or polyethylene glycol 6000 according to certain weight proportion. The present invention is used for treating vascular pathological changes and hemorrhagic diseases thereof, more specifically cerebrovascular diseases, fundus diseases, diabetic angiopathy, etc.
Description
Technical field
The present invention relates to Chinese medicine compound notoginseng dripping pills of a kind of oral administration and preparation method thereof.More particularly, the present invention relates to a kind of is the compound recipe notoginseng dripping pills of principal agent with the Chinese medicine Radix Notoginseng, and it is used for the treatment of vascular lesions and hemorrhage thereof, is meant cerebrovascular disease, retinopathy, diabetic angiopathy etc. particularly.
Background technology
Cerebrovascular is one of three big diseases that threaten human health, and its sickness rate is about 2/1000ths, and mortality rate is up to one thousandth point three, and with advancing age, its sickness rate and mortality rate all rise.Control cerebrovascular and sequela thereof are the problems of society.And along with the prolongation of human longevity, the diseases such as visual disorder due to circulatory disturbance, the ophthalmology central retinal vein occlusion such as the hypertension relevant with blood vessel and function thereof, arteriosclerosis become the key factor that has a strong impact on human life quality.Retinopathy (central retinal vein occlusion, diabetic renal papillary necrosis, senile degeneration of macula, central authorities' property retinopathy, retinal vasculitis etc.) is one of commonly encountered diseases of harm humans health, along with China's population senescence, this type of patient will increase year by year.Therefore, press for a kind of applied widely, determined curative effect, Drug therapy vascular lesions and hemorrhage thereof that safety is big.
Developed the medicine of a lot of treatment cerebrovascular abroad, but owing to be chemosynthesis, so side effect is very big.Domestic except chemosynthesis, also have Chinese herbal and crude drugs preparations.Especially over past ten years, form of Chinese drug has obtained develop rapidly, nowadays traditional ball is not only arranged, looses, dosage forms such as pellet, cream, also has dosage forms such as capsule, injection, bag bubble, oral liquid, drop pill.But the Chinese patent medicine of existing treatment cerebrovascular disease mostly is pill and capsule, a kind of treatment cardiovascular and cerebrovascular diseases medicament compositions is disclosed such as CN1253813A, this pharmaceutical composition is a capsule formulation, and it is to be prepared from by certain proportioning by the Radix Astragali, Radix Apioris Fortunei (Radix Lespedezae Buergeri), the Cortex Eucommiae, Radix Polygalae fallacis, Herba Capsellae, Radix Polygoni Multiflori Preparata, Radix Salviae Miltiorrhizae, Radix Glycyrrhizae, Radix Notoginseng.This medicine be with apoplexy at acute stage and convalescent period syndrome of blood stasis due to qi deficiency serve as the pharmaceutical composition that adapts to the treatment cardiovascular and cerebrovascular disease of disease.CN1308955A discloses a kind of natural composition of preventing and treating cardiovascular and cerebrovascular disease, this pharmaceutical composition is liquid preparation or capsule etc., and it is to be prepared from according to a certain ratio by nattokinase, Herb Gynostemmae Pentaphylli, Radix Notoginseng, Radix Salviae Miltiorrhizae, Folium Ginkgo, Radix Puerariae, Rhizoma Chuanxiong, Flos Carthami, Fructus Crataegi, sugar tolerance factor.CN1319404A discloses a kind of medicine for the treatment of coronary heart disease, and it is the medicament that is prepared into by certain proportioning with Radix Ginseng, Radix Notoginseng, the Radix Astragali, Pollen Typhae, Radix Salviae Miltiorrhizae, Radix Curcumae, and the dosage form of this medicine is tablet, powder, pill, capsule, granule, oral liquid.This medicine is that coronary heart disease, angina pectoris, myocardial infarction are had good curative effect.These Chinese herbal medicine dosage forms of prior art make trouble, and oral dose is big, the patient with after easily cause gastrointestinal upset, absorb slowly, produce effects is slow, stability of drug is poor simultaneously, bioavailability is low.Therefore, people still in the continuous new Chinese herbal medicine dosage form of more effective treatment vascular lesions of research and hemorrhage thereof, solve prior art problems, give clinical quick-acting, the medicine efficiently that many kinds are provided.
Summary of the invention
Purpose of the present invention is exactly for the new Chinese herbal medicine dosage form of a kind of good stability that cures mainly central retinal vein occlusion, cerebrovascular disease and sequela, retinopathy, diabetic angiopathy, quick-acting, efficient, low toxicity is provided.The inventor finds to select specific Chinese medicinal herbs through a large amount of tests, and the drops that its extract and specific substrate are made has solved the problems referred to above, thereby has realized purpose of the present invention.Drop pill of the present invention has many advantages, and is promptly efficient, quick-acting, long-acting, and toxicity is little, have no adverse reaction, consumption is little, good stability etc.
The invention provides a kind of Chinese medicine compound notoginseng dripping pills of oral administration, it is the medicament that is prepared from by following weight portion proportioning by Radix Notoginseng, the Radix Astragali, Radix Salviae Miltiorrhizae, Radix Scrophulariae, Macrogol 4000 or 6000:
Radix Notoginseng 200-300
Radix Astragali 70-90
Radix Salviae Miltiorrhizae 40-60
Radix Scrophulariae 70-90
Macrogol 4000 or 6000 250-450.
Chinese medicine compound notoginseng dripping pills of the present invention, Radix Notoginseng hemostasis in the side, the blood stasis dispelling promoting blood circulation, hemorrhage for controlling venation, stasis of blood resistance recovers the unimpeded principal agent of blood vessels.Radix Astragali QI invigorating, beneficial Yuanyang is taken the photograph blood.According to " the capable then blood of gas is capable ", itself and the shared QI and blood that causes of Radix Notoginseng are gone together, and unimpeded as stream makes the blood Gui Mai that is overflow, and auxilliary foster healthy energy is ministerial drug.Radix Scrophulariae: removing heat from blood, the YIN nourishing eliminating stagnation, Yi Xinmai, the heat that stasis of blood knot is produced disappears clearly.Radix Salviae Miltiorrhizae is logical to stagnate, and blood stasis dispersing and fresh blood promoting is assisted a ruler in governing a country the Radix Notoginseng blood stasis dispelling, the logical effect that stagnates, and make and outmodedly ooze out or store up that to stay blood stasis to disappear clearly be adjuvant drug altogether.More than four medicines shared, coordinate mutually, a tool is invigorated blood circulation, and controls gas, controls the treating blood disorders effect of heat, makes the venation of stasis of blood resistance smooth again, reaches the QI and blood symbiosis, the effect that blood vessels are sensible.
The specific substrate that key of the present invention also is to select the Chinese medicine medical material of best proportioning and selects suitable this Chinese medicine medical material has made it synergy, has increased stability of drug, makes the dissolution of drop pill reach quick-acting simultaneously.In addition, the proportioning of medicine and substrate is also quite important, and it can influence hardness, the dissolve scattered time limit of drop pill.Through experimentation repeatedly, optimum substrate is Macrogol 4000 or 6000, and is preferred, polyethylene glycol 6000.
The Chinese medicine compound notoginseng dripping pills of the most preferred a kind of oral administration of the present invention, it is the medicament that is prepared from by following weight portion proportioning by Radix Notoginseng, the Radix Astragali, Radix Salviae Miltiorrhizae, Radix Scrophulariae, Macrogol 4000 or 6000:
Radix Notoginseng 250
The Radix Astragali 80
Radix Salviae Miltiorrhizae 50
Radix Scrophulariae 80
Macrogol 4000 or 6,000 360.
Below describe the preparation technology of compound recipe notoginseng dripping pills of the present invention in detail:
(1) preparation of extract: the Radix Notoginseng in the above-mentioned four Chinese medicine is pulverized, with 50-60% alcohol dipping twice, 4-6 days for the first time, 1-2 days for the second time, filter, merging filtrate reclaims ethanol, is condensed into thick paste, oven dry is ground into fine powder, sieves, and all the other Radixs Astragali etc. three flavor is with twice of 50-60% alcohol heating reflux, 2-3 hour for the first time, 1-2 hour for the second time, filter merging filtrate, reclaim ethanol, spray drying becomes fine powder, with above-mentioned fine powder mixing, sieve, standby.
(2) fusion: taking polyethylene glycol 4000 or 6000, be heated to 80-90 ℃ and make moltenly, above-mentioned fine powder mixture is added, stir fusion, and be incubated 85 ℃.
(3) drip system: with above-mentioned mixed liquor, pour in the drop pill device, 85 ℃ of water bath heat preservations splash in 5 ℃ the liquid paraffin, after the system of dripping finishes drop pill are continued to stay in the coolant, and it is fully cooled off, and take out, and inhale and remove surface liquid paraffin, drying, promptly.
Compound recipe notoginseng dripping pills of the present invention through this prepared has good dissolution, and the bioavailability height has improved relieving effect and reduced deactivation in the body, has increased stability of drug simultaneously, makes medicine can reach quick-acting.
The pharmacological action of Chinese medicine compound notoginseng dripping pills of the present invention is a blood circulation promoting and blood stasis dispelling, blood vessel dilating, and blood flow increasing reduces myocardial oxygen consumption, improves blood circulation and microcirculation, the supplementing QI and nourishing YIN effect.Its mechanism of action is to shorten clotting time, promotes clot dissolution, and antithrombotic forms, and increases the peripheral blood vessel perfusion flow, increases the carotid artery flow amount, increases Mesenteric artery and venous bore.Therefore, Chinese medicine compound notoginseng dripping pills of the present invention can be used for treating blood stasis the hold concurrently sudden blindness (retinal vein occlusion) and the blurring of vission (central serous chorioretinopathy) of syndrome of deficiency of both qi and yin.
The clinical studies data shows, oral administered compound notoginseng dripping pills preparation can be treated blood stasis the hold concurrently retinal vein occlusion and the central serous chorioretinopathy of deficiency of both QI and YIN disease, has blood circulation promoting and blood stasis dispelling, the effect of supplementing QI and nourishing YIN, patient's vision is improved and is improved, angry the opening of eyeground vein alleviates, retinal hemorrhage absorbs and disappears, the visible venous filling time of fluorescence fundus angiography shortens, vascular leakage is eliminated or is alleviated, and cystoid macular edema disappears, and retina oozes out absorption, optical fundus central fovea luminous reflectance reappears, and fluorescence fundus angiography does not see that seepage or seepage degree alleviate; Treatment branch retinal obstruction of artery, it is satisfactory that central vision recovers; Treatment of diabetic retinopathy becomes certain effect, individual patients is had the curative effect of highly significant; The treatment angina pectoris improves the clinical symptoms total effective rate more than 80%.So, clinically, compound recipe notoginseng dripping pills of the present invention is used for the treatment of the retinopathy due to (1) optical fundus blood vessel disease, (2) central serous chorioretinopathy, (3) traumatic hyphema, (4) retinal artery occlusion, (5) diabetic renal papillary necrosis, (6) angina pectoris etc.
Compound recipe notoginseng dripping pills of the present invention is treated retinopathy clinically, effect observation, and 300 eyes of oral compound recipe notoginseng dripping pills treatment retinopathy 213 examples of the present invention, total effective rate reaches 82.5%.Wherein central retinal vein occlusion 41 examples are 41, effective percentage 90.2%; 81 of diabetic retina 41 examples, effective percentage 79.0%; 88 of senile degeneration of macula 50 examples, effective percentage 82.7%; 38 of central retina pathological changes 37 examples, effective percentage 97.1%.
The specific embodiment
Below adopt embodiment to specify compound recipe notoginseng dripping pills of the present invention and preparation method thereof.
Embodiment 1
A kind of Chinese medicine compound notoginseng dripping pills of oral administration, it is the medicament that is prepared from by following weight proportion by Radix Notoginseng, the Radix Astragali, Radix Salviae Miltiorrhizae, Radix Scrophulariae, Macrogol 4000 or 6000:
Radix Notoginseng 250 grams
The Radix Astragali 80 grams
Radix Salviae Miltiorrhizae 50 grams
Radix Scrophulariae 80 grams
Macrogol 4000 or 6,000 360 grams.
Its preparation method is as follows:
(1) preparation of extract: the Radix Notoginseng in the above-mentioned four Chinese medicine is pulverized, with 50% alcohol dipping twice, 5 days for the first time, 2 days for the second time, filter, merging filtrate reclaims ethanol, is condensed into thick paste, oven dry is ground into fine powder, sieves, and all the other Radixs Astragali etc. three flavor is with twice of 50% alcohol heating reflux, 3 hours for the first time, 2 hours for the second time, filter merging filtrate, reclaim ethanol, spray drying becomes fine powder, with above-mentioned fine powder mixing, sieve, standby.
(2) fusion: taking polyethylene glycol 6000, be heated to 85 ℃ and make moltenly, above-mentioned fine powder mixture is added, stir fusion, and be incubated 85 ℃.
(3) drip system: with above-mentioned mixed liquor, pour in the drop pill device, 85 ℃ of water bath heat preservations splash in 5 ℃ the liquid paraffin, after the system of dripping finishes drop pill are continued to stay in the coolant, and it is fully cooled off, and take out, and inhale and remove surface liquid paraffin, drying, promptly.
Compound recipe notoginseng dripping pills of the present invention has many advantages, be triple effect (efficient, quick-acting, long-acting), three little (toxicity, reaction, consumption are little) and five convenience (produce, transport, use, carry, keeping convenient), it is compared with solid preparations such as the sheet of existing treatment angiopathy, capsules, drug effect is remarkable, bioavailability improves, and stability strengthens, and has really reached quick-acting, purpose efficiently.Randomized controlled trial shows that oral compound recipe notoginseng dripping pills of the present invention is better than the curative effect that existing FUFANG DANSHEN PIAN adds SHENGMAI YIN KOUFUYE.Advantages such as that compound recipe notoginseng dripping pills of the present invention has is easy to use, have no side effect, this makes this medicine will bring into play bigger effect clinically, for clinical application provides a kind of novel form, to be fit to requirement of different patients.
Below further specify the drug action of compound recipe notoginseng dripping pills of the present invention by pharmacodynamics test:
According to " study of tcm new drug guide ", the pharmacodynamics test of compound recipe notoginseng dripping pills of the present invention comprises following content:
Observed the compound recipe notoginseng dripping pills to the dissolving of white mice clotting time, rats in vitro blood clot, the influence that the rat thrombus in vivo forms; Observed of rat blood viscosity, erythrocyte sedimentation rate, the influence of platelet aggregation time of compound recipe notoginseng dripping pills to acute blood stasis and high blood viscosity model; Also observed of rat ridge oblique and the rabbit conjunctive bulbi microcirculatory influence of compound recipe notoginseng dripping pills to high polysaccharide model.The result is reported as follows.
Experiment material
One, medicine: the agent of compound recipe notoginseng dripping pills provides (2.5 crude drugs/g), be diluted to desired concn with normal saline by Guangdong Gaosheng medicine Development Co., Ltd.
Two, general reagent: heparin (Wanbang Biochemically Pharmaceutical Co Ltd, Xuzhou), normal saline (Anhui Huayuan Biological Pharmaceutical Industry Co., Ltd.), urethane (Shanghai biochemical reagents company), chloralose (Fluka), macromolecule right rotary glycoside (molecular weight 413 263 dalton, U.S. Sigma), pentobarbital sodium (Uni0n, the Shanghai packing), sodium citrate (Shanghai biochemical reagents company), adenosine diphosphate (ADP) (ADP, U.S. Sigma), adrenalin hydrochloride injection (Shanghai Hefeng Pharmaceutical Co., Ltd.), plasma fibrinogen is measured test kit (kind city, Ningbo City biochemical reagents factory).(1ml silicone oil, ether adds to 100ml to 1% methyl-silicone oil-diethyl ether solution.Ether is a chemical pure, and Changsha prolongs air slaking chemical reagent work, lot number: 910117).
Three, instrument and apparatus: LG-R-80 (A) type blood viscometer (Beijing Steellex Scientific Instrument Company), LG-PABER type platelet aggregation thrombin analyser (Beijing Steellex Scientific Instrument Company), erythrocyte correlation tracking instrument (American I PM), TV micrometer (For A Japan), microscopic system (Hitachi, Japan), XSN-RII type external thrombus formation/platelet adhesion double-purpose instrument (Wuxi County electronic machine two factories), the silication syringe, 10ml long-neck glass pin, disposable 20 μ l blood taking tubes, blood counting chamber, microscope.Electronic balance, general operating theater instruments etc.
Four, use animal: the SD rat, body weight 200-350 gram, male and female half and half are provided by No.1 Military Medical Univ.'s Experimental Animal Center, and the animal quality certification number is Guangdong searching 2000A1111 number; The KM mice, 30-50 gram is provided by No.1 Military Medical Univ.'s Experimental Animal Center, and the animal quality certification number is Guangdong searching 2000A058.New zealand white rabbit, male and female are regardless of, and are provided by No.1 Military Medical Univ.'s Experimental Animal Center and laboratory animal room of Guangzhou General Hospital Guangzhou Military Command respectively, and the animal quality certification number is respectively the Guangdong searching ... ... and 2000A057.
Five, statistical method: data representation is mean ± standard deviation, adopts the SPSS-10.0 statistical software that each group data is carried out one factor analysis of variance (One Way ANOVA), and the thrombolytic rate between external each group of thrombolytic effect experiment is relatively checked with Friedman.There is statistical significance P＜0.05 for difference
Method and result
One, the compound recipe notoginseng dripping pills is to the influence of white mice clotting time
50 of white mice, random packet, 10 every group.Clotting time of mice is measured the capillary glass-tube method that adopts, glass capillary (internal diameter 1mm, long 10cm), each treated animal gastric infusion is after 1 hour, cutting off mousetail (terminal 0.5cm place) extrudes 2 and bleeds on sheet glass, immediately blood is sucked in the glass capillary, begin to clock after lying against desktop, the about 0.5cm of an end capillary tube fractureed every 30 seconds after two minutes, and slowly draw back to the left and right, whether the observation place of fractureing has the blood clotting silk, till occurring to the blood clotting silk, is clotting time between institute lasts.
The result shows, the big or middle dosage group energy of compound recipe notoginseng dripping pills significant prolongation clotting time of mice (P＜0.05); Compound recipe notoginseng dripping pills small dose group can prolong clotting time of mice (P＜0.01) very significantly.The results are shown in Table
Table 1: the compound recipe notoginseng dripping pills is to the influence of clotting time of mice
| Group | Dosage (mg/kg) | Clotting time (s, x ± s) |
| Dosage group drop pill small dose group in the heavy dose of group of the normal saline drop pill drop pill | Isometric(al) 240 168 117.6 | 313±66 411±61* 424±81* 472±134** |
Annotate: compare * P＜0.05, * * P＜0.01 with the normal saline matched group.
Two, the compound recipe notoginseng dripping pills coagulates the dissolution of determining to the rat extracorporeal blood
After rat is weighed,, anaesthetize by the dosage of 0.6ml/100gb.wt. with the chloralose of 13.3% urethane and 0.5%, row one side common carotid artery intubate, extract the non-anticoagulant arterial blood of 0.6ml, respectively get 0.3ml and inject two centrifuge tubes rapidly, treat carefully to take out behind its clot that congeals into, blot the liquid part of being infected with, use scales/electronic balance weighing, blood clot is reloaded two centrifuge tubes, by grouping, add relative medicine 1ml, matched group only adds the equivalent normal saline.Room temperature leaves standstill after 24 hours and takes out, blots the liquid part of being infected with, and uses scales/electronic balance weighing, relatively the weight of blood clot before and after the administration.
The result shows that compound recipe notoginseng dripping pills dosage form has tangible dissolution to sludged blood.The big minispread of its dissolution is respectively heavy dose of compound recipe notoginseng dripping pills best (having dissolved 34.87mg), be the compound recipe notoginseng dripping pills agent (dissolved respectively 31.24 and 27.38mg) of low dosage and middle dosage then, normal saline group thrombolytic effect the poorest (only having dissolved 18.03mg), the difference between each medication group have remarkable statistical significance (Friedman checks p＜0.05).
The external thrombolytic effect of the compound recipe Radix Notoginseng of table 2. various dose relatively
| Grouping | Drug dose (mg/1ml | The example number | Dissolution rate to every 80mg sludged blood | The ordering coefficient * of Friedman check |
| ) | (mg，x±s) | |||
| Dosage group drop pill small dose group in the heavy dose of group of the normal saline drop pill drop pill | Isometric(al) 14 9.8 6.86 | 13 13 13 13 | 18.03±12.61 34.87±17.56 27.38±13.02 31.24±15.36 | 1.77 3.46 2.62 3.31 |
* the ordering coefficient of Friedman check is big more, illustrates that solute effect is good more, and the difference between each group has remarkable statistical significance (p＜0.05).
Three, the compound recipe notoginseng dripping pills is to the influence of rat thrombus in vivo formation
The 1-0 silk thread is soaked the back with scales/electronic balance weighing and record with normal saline, silk thread is penetrated in the polyethylene tube, 1cm is respectively stayed at two ends, and pours into the 60u/ml heparin, and it is standby to make intubate.Get 50 of the SD rats of 300-400 gram, be divided into 5 groups at random, 10 every group.Give rat oral gavage according to dose (1ml/100g b.wt), irritate behind the stomach chloralose intraperitoneal injection of anesthesia with 13.3% urethane and 0.5%.Separate rat one side common carotid artery and offside external jugular vein, ready polyethylene catheter two ends are inserted common carotid artery and external jugular vein respectively, note external the end of a thread, and keep the bulldog clamp closed condition.After waiting to irritate stomach 1h, open bulldog clamp, allow blood flow naturally by intubate, form arteriovenous shunt, folder closes common carotid artery behind the 15min, takes out silk thread and blood clot in the intubate rapidly, blots the back and uses scales/electronic balance weighing, deducts the silk thread weight in wet base, is wet weight of thrombus.The result shows that each group of compound recipe notoginseng dripping pills dosage form all has the obvious suppression effect to the formation of thrombus in vivo, compares with the normal saline group, and thrombus weight obviously alleviates, and remarkable statistical significance (P＜0.05) is arranged.The results are shown in Table 3.
The inhibitory action that the compound recipe Radix Notoginseng of table 3. various dose forms thrombus in vivo
| Grouping | Drug dose (g/kg) | The example number | Thrombus weight (mg, x ± s) |
| Dosage group drop pill small dose group in the heavy dose of group of the normal saline drop pill drop pill | Isometric(al) 0.14 0.098 0.0686 | 10 10 10 10 | 14.31±3.61 11.08±3.32* 11.38±2.14*§ 11.48±2.89*§ |
* compare P＜0.05 with the blank group.
Four, the compound recipe notoginseng dripping pills is to the influence of rats in vitro platelet aggregation
Get 14 of SD rats, male and female are regardless of.The SD rat of fasting after 12 hours anaesthetized with pentobarbital sodium, the anesthesia amount is 30mg/kg, open abdomen, the about 8ml of ventral aorta blood sampling, with 3.8% sodium citrate anticoagulant (blood and anticoagulant dosage volume ratio are 9: 1), the centrifugal 5min of 800r/min, take out platelet rich plasma (platelet richplasma, PRP), again with the centrifugal 10min of 3000r/min, draw platelet poor plasma (platelet poorplasma, PPP), get 20ul medicine and 300ul PRP in 37 ℃ of incubation 3min, the blank group is given 20ul physiologic saline for substitute medicine.To wait capacity PPP to compare, add 10umol/LADP as luring poly-agent, measure platelet aggregation percentage rate in the 5min, the maximum percentage rate of assembling of platelet in the record 5min, the blood preparation of each routine animal is all carried out the detection of 5 groups respectively.All experiment was finished in 2 hours.
The result shows that the compound recipe notoginseng dripping pills group of various dose does not all have significantly influence to the rats in vitro platelet aggregation, and the statistical procedures demonstration is compared with the normal saline group does not all have remarkable type difference.
Table 4: the compound recipe Radix Notoginseng of different dosage form and dosage is to the influence of rats in vitro platelet aggregation
| Group | Dosage (20ul, mg/ml) | The example number | Platelet maximum agglutination rate (%) (x ± s) |
| Dosage group drop pill small dose group in the heavy dose of group of the normal saline drop pill drop pill | Isometric(al) 14 9.8 6.86 | 14 14 14 14 | 38.2±12.6 37.5±7.0 37.3±9.2 39.8±11.2 |
Compare there was no significant difference between each group.
Five, the compound recipe Radix Notoginseng is to the influence of rabbit platelet adhesion
Get 25 of new zealand rabbits, male, body weight 34Kg.Every group with 5 of animals, totally 5 groups, be respectively the normal saline matched group, the heavy dose of group of compound recipe notoginseng dripping pills (0.1g/Kg), middle dosage group (0.07g/Kg), low dose group (0.049g/Kg) and.Do not anaesthetize heart extracting blood, behind the mensuration platelet adhesion, by above-mentioned dosage gastric infusion or isometric(al) normal saline.Got blood check platelet adhesion after the administration in 1 hour again.The platelet adhesion assay method
[1]: (1) connects instrument power source, opens the temperature control switch, will measure temperature stabilization at 37 ℃.(2) get blood 7.8ml with the silication syringe, add mixing in the silication scale test tube of 3.8% sodium citrate 0.2ml.(3) inhale the 1.5ml anticoagulation with 2ml silication measuring pipette, inject 10ml long-neck glass pin, put it into the platelet adhesion analyzer, with 3.5 rev/mins of speed, pin is taken off in rotation in 15 minutes, draw before adhering to respectively and the blood sample after adhering to, make platelet count
[2], calculate platelet adhesion rate by following formula.
Experimental result shows that the compound recipe notoginseng dripping pills of high dose and middle dosage has the effect of remarkable reduction platelet adhesion rate.See the following form.
The agent of table 5. compound recipe notoginseng dripping pills is to the adhering influence of rat platelet (x ± s)
| Group | Dosage (g/Kg) | Number of animals | Platelet adhesion rate (%) | |
| Before the administration | After the administration | |||
| Dosage group drop pill small dose group in the heavy dose of group of the normal saline drop pill drop pill | Isometric(al) 0.1 0.07 0.049 | 5 5 5 5 | 39.28±12.55 35.90±9.88 38.18±5.59 44.50±6.49 | 39.36±14.82 23.68±5.66* 30.64±2.12* 37.20±7.51 |
Annotate: with before the administration relatively: * P＜0.05.
Six, the compound recipe notoginseng dripping pills is to the influence of stasis syndrome model (adrenalin hydrochloride and ice-water bath modeling) hemorheology of rat and platelet aggregation
Animal modeling and detection method: animal is carried out medicine irritate stomach, volume is the 1ml/100g rat body weight, irritates stomach every day 1 time, irritate stomach beginning in the 7th day modeling (except the normal control group), not drug withdrawal during the modeling of administration group, fasting 12 hours before blood sampling in the 9th day, the administration 1 time again in preceding 1 hour of taking a blood sample.
Animal is in irritating stomach the 7th day, the adrenalin hydrochloride of subcutaneous injection 0.1% (0.08ml/100g rat body weight), continuous 2 days, every day 2 times, to be separated by 6 hours for twice, double injection interim was soaked rat 5 minutes with frozen water, last subcutaneous injection epinephrine is after 18 hours, abdomen is opened in lumbar injection 2.25% pentobarbital sodium (30mg/kg) anesthesia then, the ventral aorta blood sampling.Detect whole blood viscosity, plasma viscosity and fibrinogen content, erythrocyte sedimentation rate, hematocrit and platelet aggregation rate respectively.
Blood is used sodium citrate (blood is 9: 1 with the ratio of the anticoagulant) anticoagulant of heparin sodium (40 μ anticoagulant 1ml blood) and 3.8% respectively, and heparin sodium anticoagulation (5ml) detects whole blood viscosity, erythrocyte sedimentation rate and hematocrit.Separate (the centrifugal 10min of 3000r/min) blood plasma and detect plasma viscosity, fibrinogen content, whole blood and plasma viscosity adopt blood viscosity instrument to measure, and plasma fibrinogen adopts kit measurement.The detection of erythrocyte sedimentation rate is to inject whole blood (the injection blood level is 10cm) in the hematocrit pipe, places 1 hour in 37 ℃ of calorstats, reads the erythrocyte sedimentation rate data; Packed cell volume adopts centrifuging, injects whole blood in the hematocrit pipe, after centrifugal (3000r/min15 minute), reads the packed cell volume percentage rate; Behind the sodium citrate anticoagulation (3ml) centrifugal (the centrifugal 5min of 800/min), take out platelet rich plasma (PRP), again with the centrifugal 10min of 3000r/min, draw platelet poor plasma (PPP), return to zero with PPP (300ul), add ADP and lure in the PRP (300ul) of poly-agent (10umol/L) after pre-temperature (37 ℃ of 3min), the employing platelet aggregation instrument is measured the platelet aggregation percentage rate in 5 minutes, writes down the maximum percentage rate of assembling of platelet in 5 minutes.
The result shows, compare with model group, the heavy dose of group of compound recipe notoginseng dripping pills can significantly reduce whole blood viscosity (P＜0.05 under the different shear rates of acute blood stasis animal, P＜0.01), reduction viscosity of blood (P＜0.01), the maximum percentage rate of assembling of platelet is also had certain inhibitory action (P=0.091, near significantly); Dosage can significantly reduce high shear rate (30/S in the compound recipe notoginseng dripping pills, (P＜0.05 of whole blood viscosity 150/S), P＜0.01), the dosage group also has certain inhibitory action (P=0.076 is near remarkable) to the maximum percentage rate of assembling of platelet in reduction viscosity of blood (P＜0.05), the compound recipe notoginseng dripping pills; Compound recipe notoginseng dripping pills small dose group has significant reduction effect (P＜0.05, P＜0.01), can reduce reduction viscosity of blood (P＜0.01) very significantly the whole blood viscosity of different shear rates (5/S, 30/S, 150/S).The compound recipe notoginseng dripping pills is to not significantly influence of sedimentation indices.The results are shown in Table 6-9
Table 6. compound recipe notoginseng dripping pills is to the influence of stasis syndrome rat model blood viscosity (x ± s)
| Group | Drug dose (g/kg) | Different shear rate whole blood viscosity (mPas) | |||
| 1/S | 5/S | 30/S | 150/S | ||
| Dosage group dripping pill small dose group in the heavy dose of group of the normal group physiological saline group dripping pill dripping pill | Isometric(al) NS isometric(al) 0.14 0.098 0.0686 | 14.24±2.35 18.28±4.17 ΔΔ 15.28±2.41 * 17.01±3.61 Δ 16.76±2.34 | 8.85±1.09 11.13±2.04 ΔΔ 9.30±1.35* * 10.04±1.72 9.85±1.20* | 6.72±0.67 8.37±1.34 ΔΔ 6.95±1.00* * 7.41±1.10* 7.19±0.80* * | 5.98±0.54 7.43±1.13Δ Δ 6.15±0.86** 6.49±0.89** 6.36±0.64** |
Annotate: 1. compare with normal group: Δ P＜0.05, Δ Δ P＜0.01.2. compare with model group: * P＜0.05, * * P＜0.01.
Table 7. compound recipe notoginseng dripping pills is to the influence of stasis syndrome rat model packed cell volume and whole blood reduced viscosity (x ± s)
| Group | Drug dose (g/kg) | Packed cell volume (L/L) | Reduction viscosity of blood | The low reduced viscosity of cutting of whole blood |
| Dosage group dripping pill small dose group in the heavy dose of group of the normal group physiological saline group dripping pill dripping pill | Isometric(al) NS isometric(al) 0.14 0.098 0.0686 | 0.44±0.03 0.45±0.05 0.44±0.03 0.44±0.04 0.45±0.04 | 11.35±1.69 14.19±2.37Δ Δ 11.60±1.92** 12.46±1.32* 11.86±1.26** | 30.22±6.49 38.23±9.49Δ Δ 32.13±5.10 36.18±5.70Δ 34.77±3.43 |
Annotate: 1. compare with normal group: Δ P＜0.05, Δ Δ P＜0.01.2. compare with model group: * P＜0.05, * * P＜0.01.
Table 8. compound recipe notoginseng dripping pills is to the influence of stasis syndrome rat model sedimentation indices (x ± s)
| Group | Drug dose (g/kg) | Erythrocyte sedimentation rate mm/h | The erythrocyte rigidity index | Erythrocyte aggregation index | ESR equation K value |
| Dosage group dripping pill small dose group in the heavy dose of group of the normal group physiological saline group dripping pill dripping pill | Isometric(al) NS isometric(al) 0.14 0.098 0.0686 | 2.1±1.6 2.8±2.7 1.5±0.9 1.5±1.0 2.0±2.2 | 5.09±1.62 4.80±2.30 3.66±1.33 Δ 3.78±1.41 3.43±1.59 Δ | 2.37±0.23 2.45±0.31 2.48±0.16 2.60±0.23 Δ 2.63±0.19 Δ | 7±6 13±20 5±3 5±4 7±6 |
Annotate: 1. compare with normal group: Δ P＜0.05, Δ Δ P＜0.01.2. compare with model group: * P＜0.05, * * P＜0.01.
Table 9. compound recipe notoginseng dripping pills is to stasis syndrome rat model plasma fibrinogen content and platelet aggregation
Influence (x ± s)
| Group | Drug dose (g/kg) | Fibrinogen (g/L) | Plasma viscosity (mPas) 100/S | The maximum percentage rate (%) of assembling of platelet |
| Dosage group dripping pill small dose group in the heavy dose of group of the normal group model group dripping pill dripping pill | Isometric(al) NS isometric(al) 0.14 0.098 0.0686 | 1.07±0.39 3.71±1.15ΔΔ 3.76±1.29ΔΔ 3.16±1.46ΔΔ 3.40±1.15ΔΔ | 1.90±0.30 2.61±1.02Δ 2.48±0.75Δ 2.56±0.68Δ 2.43±0.48 | 37.0±9.0 44.2±18.7 35.5±14.0 35.0±8.6 37.1±11.1 |
Annotate: 1. compare with normal group: Δ P＜0.05, Δ Δ P＜0.01.2. compare with model group: * P＜0.05, * * P＜0.01.
Seven, the compound recipe notoginseng dripping pills is to the influence of high blood viscosity model (macromolecule right rotary glycoside modeling) hemorheology of rat and platelet aggregation rate
The animal fasting is gastric infusion after about 12 hours, cross about 1 hour, with 13.3% urethane+0.5% Chloralosane mixed liquor anesthesia, separate femoral vein, insert femoral vein with the PE50 polyethylene tube, irritated first behind the stomach 2 hours, (mean molecule quantity is 413 to import 10% high molecular dextran 0.6ml/100g.bw.t by femoral vein, 263 dalton), gastric infusion 1 time more simultaneously.After 2 hours, the ventral aorta blood sampling.Detect whole blood viscosity, plasma viscosity and fibrinogen content, erythrocyte sedimentation rate, packed cell volume and platelet aggregation rate as stated above.
The result shows, compare with model group, compound recipe notoginseng dripping pills small dose group can significantly reduce the whole blood viscosity (P＜0.01, P＜0.05) under the different shear rates of high blood viscosity animal pattern, can significantly reduce the low reduced viscosity (P＜0.05, P＜0.01) of cutting of reduction viscosity of blood and whole blood; Small dose group erythrocyte rigidity index is starkly lower than model group (P＜0.05).The results are shown in Table 10-13.
Table 10. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat model blood viscosity (x ± s)
| Group | Drug dose (g/kg) | Different shear rate whole blood viscosity (mPas) | |||
| 1/S | 5/S | 30/S | 150/S | ||
| Normal group | Isometric(al) NS | 14.24±2.3 5 | 8.85±1.09 | 6.72±0.67 | 5.98±0.54 |
| Dosage group dripping pill small dose group in the heavy dose of group of the physiological saline group dripping pill dripping pill | B isometric(al) 0.140 0.098 0.0686 | 22.96±6.5 9 20.66±3.6 1 21.27±4.7 1 17.34±4.5 5** | 13.53±3.42 12.53±2.15 12.68±2.75 10.52±2.59 ** | 9.91±2.31 9.36±1.68 9.36±2.07 7.86±1.88* | 8.67±1.96 8.28±1.54 8.23±1.86 6.94±1.65* |
Annotate: 1. compare with normal group: Δ P＜0.05, Δ Δ P＜0.01.2. compare with model group: * P＜0.05, * * P＜0.01.
Table 11. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat model packed cell volume and whole blood reduced viscosity (x ± s)
| Group | Drug dose (g/kg) | Packed cell volume (L/L) | Reduction viscosity of blood | The low reduced viscosity of cutting of whole blood |
| Dosage group dripping pill small dose group in the heavy dose of group of the normal group physiological saline group dripping pill dripping pill | Isometric(al) NS isometric(al) 0.140 0.98 0.686 | 0.44±0.03 0.53±0.05 0.53±0.07 0.57±0.06 0.51±0.08 | 11.35±1.69 14.73±4.15Δ Δ 13.63±2.03 12.64±2.30 11.70±3.21* | 30.22±6.49 42.38±14.79 ΔΔ 36.91±5.05 35.52±6.02 31.98±8.01** |
Annotate: 1. compare with normal group: Δ P＜0.05, Δ Δ P＜0.01.2. compare with model group: * P＜0.05, * * P＜0.01.
Table 12. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat model sedimentation indices (x ± s)
| Group | Drug dose (g/kg) | Erythrocyte sedimentation rate mm/h | The erythrocyte rigidity index | Erythrocyte aggregation index | ESR equation K value |
| Normal group normal saline group | Isometric(al) NS isometric(al) | 2.1±1.6 3.0±3.0 | 5.09±1.62 5.21±2.88 | 2.37±0.23 2.63±0.29 | 7±6 18±19 |
| Dosage group drop pill small dose group in the heavy dose of group of the drop pill drop pill | 0.140 0.98 0.686 | 2.2±2.0 2.9±2.7 3.9±5.3 | 4.40±1.87 3.92±1.43 3.16±1.53* | 2.51±0.30 2.60±0.29 2.49±0.24 | 14±12 22±19 20±21 |
Annotate: 1. compare with normal group: Δ P＜0.05, Δ Δ P＜0.01.2. compare with model group: * P＜0.05, * * P＜0.01.
Table 13. compound recipe notoginseng dripping pills is to high blood viscosity rat model plasma fibrinogen content and plasma viscosity
Influence (x ± s)
| Group | Drug dose (g/kg) | Fibrinogen (g/L) | Plasma viscosity (mPas) 100/S |
| Dosage group dripping pill small dose group in the heavy dose of group of the normal group physiological saline group dripping pill dripping pill | Isometric(al) NS isometric(al) 0.140 0.98 0.686 | 1.07±0.39 0.61±0.14ΔΔ 0.65±0.19 0.69±0.41 0.79±0.35 | 1.90±0.30 2.58±0.96 2.65±0.88 2.70±0.84 2.76±0.70 |
Annotate: 1. compare with normal group: Δ P＜0.05, Δ Δ P＜0.01.2. compare with model group: * P＜0.05, * * P＜0.01.
Eight, the compound recipe notoginseng dripping pills influences high blood viscosity model (macromolecule right rotary glycoside modeling) microcirculation of rats
About 12 hours gastric infusions of animal fasting with 13.3% urethane+0.5% Chloralosane intraperitoneal injection of anesthesia, separated femoral vein after 1 hour, inserted femoral vein with the PE50 polyethylene tube, pressed Gray
[3]Legal system is equipped with rat ridge oblique live body microcirculation and observes specimen, and it is constant to keep specimen environment (temperature and acid-base value) with 37 ℃ of Krebs stream of liquid droplets.Irritate first behind the stomach and to import 10% high molecular dextran 0.6ml/100g.bw.t from vein in 2 hours, and gastric infusion once more, various medicines given respectively according to dosage.Long with Leitz apart from camera lens, the O1ympus microscope, colored micro tv of Hitachi and measuring system are carried out viviperception, are amplifying the observation 3rd level arteriole (A of branch under 4000 times of conditions
3) and thin vein (V
3) bore, with the erythrocyte speed (V in 102 type erythrocyte tracking correlators (American I PM company product) the measurement blood flow
RBC) calculating parameter: mean blood flow velocity Vmean=V as follows
RBC/ 1.6, and blood flow (Blood flow, BF)=Vmean* π * D
2/ 4, wherein D is an external caliber.Write down respectively that dextran injects before the back and back 15 minutes and administration after 60 minutes microcirculation numerical value.
The result shows that after the macromolecule right rotary glycoside modeling, the bore of rat ridge oblique arteriole and venule does not all have significantly to change; But the flow velocity of artery and vein all obviously slows down, thereby causes the obvious reduction of artery and vein flow.After giving the drop pill of saline or various dose, the flow velocity of arteriole and venule and flow all obtain recovery in various degree.Do not have statistical significance though the medication group is compared difference with model group, the recovery amplitude of blood flow rate and blood flow is bigger slightly than model group.The result sees table 15-20 for details.
Table 15. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat arteriole bore (μ m, x ± s)
| Grouping | Drug dose (g/kg) | Normally | Give 15min behind the dextran | After the administration 6 ' |
| Dosage group drop pill small dose group in the heavy dose of group of the normal saline group drop pill drop pill | Isometric(al) 0.140 0.98 0.686 | 27.13±1.25 27.38±1.19 27.38±1.30 27.00±1.51 | 27.38±1.77 27.63±1.60 27.75±1.75 27.50±1.69 | 27.25±1.83 27.63±1.41 27.63±1.41 27.38±1.41 |
Table 16. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat arteriole flow velocity (mm/s, x ± s)
| Grouping | Drug dose (g/kg) | Normally | Give 15min behind the dextran | After the administration 60 ' |
| Dosage group drop pill small dose group in the heavy dose of group of the normal saline group drop pill drop pill | Isometric(al) 0.140 0.98 0.686 | 4.86±0.34 4.94±0.33 4.93±0.42 4.83±0.54 | 0.61±0.21 0.64±0.18 0.65±0.21 0.66±0.24 | 1.25±0.47*# 1.39±0.45*# 1.44±0.52*# 1.44±0.51*# |
Own control: * and normal phase be than p＜0.01, # with give dextran after 15min compare p＜0.01.The justice of below respectively expressing the meaning is identical.
Table 17. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat arteriole flow (pl/s, x ± s)
| Grouping | Drug dose (g/kg) | Normally | Give 15min behind the dextran | After the administration 60 ' |
| Dosage drop pill small dose group in the heavy dose of drop pill of normal saline group drop pill | Isometric(al) 0.140 0.98 0.686 | 1749.41±64.71 1810.09±72.28 1803.21±75.74 1717.90± | 219.14±58.74 235.60±45.55 239.28±57.28 240.95±70.97 | 440.52± 508.56± 526.64± 517.25± |
Table 18. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat venule bore (μ m, x ± s)
| Grouping | Normally | Give 15min behind the dextran | After the administration 60 ' |
| Dosage drop pill small dose group in the heavy dose of drop pill of normal saline group drop pill | 27.75±1.04 27.50±1.20 27.63±1.06 27.63±1.19 | 28.63±1.19 28.50±1.51 28.63±1.06 28.88±1.46 | 28.13±1.13 28.25±1.16 28.25±1.04 28.25±1.49 |
Table 19. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat venule flow velocity (mm/s, x ± s)
| Grouping | Drug dose (g/kg) | Normally | Give 15min behind the dextran | After the administration 60 ' |
| Dosage group drop pill small dose group in the heavy dose of group of the model group drop pill drop pill | Isometric(al) 0.140 0.98 0.686 | 1.88±0.28 1.93±0.27 1.91±0.24 1.90±0.34 | 0.16±0.08 0.18±0.07 0.18±0.09 0.20±0.13 | 0.45±0.10*# 0.52±0.15*# 0.51±0.14*# 0.53±1.49*# |
Table 20. compound recipe notoginseng dripping pills is to the influence of high blood viscosity rat venule flow (pl/s, x ± s)
| Grouping | Drug dose (g/kg) | Normally | Give 15min behind the dextran | After the administration 60 ' |
| Dosage group drop pill small dose group in the heavy dose of group of the model group drop pill drop pill | Isometric(al) 0.140 0.98 0.686 | 704.03±68.32 709.39±56.69 711.71±48.38 703.45±71.03 | 63.82±27.13 71.24±25.65 71.79±32.03 78.64±44.08 | 171.12± 200.34± 199.55± 202.60± |
Nine, the compound recipe notoginseng dripping pills is to the influence of high blood viscosity model (macromolecule right rotary glycoside modeling) rabbit bulbar Conjunctiva Microcirculation
Rabbit fasting 12 hours by various dosage gastric infusions, was pressed 1ml/kg auricular vein injecting anesthetic with 3% pentobarbital sodium in 1.5 hours after the administration.After the animal rabbit platform is fixing, cut off eyelash, eyelid threading tractive exposes eyeball, places on the bulbar Conjunctiva Microcirculation observation platform.Observe and write down microcirculatory fluidised form by optical microscope and microscope camera system, obtain qualitative index; Irritate first behind the stomach and to inject 10% macromolecule right rotary glycoside by auricular vein according to the amount of 15ml/kg in 2 hours, simultaneously gastric infusion once more.Observing microcirculation after 20 minutes changes.Carried out the observation of bulbar Conjunctiva Microcirculation after the last administration in 1 hour.The result shows that normal rabbit bulbar Conjunctiva Microcirculation flow velocity is very fast, and blood flow becomes uniform line grain stream.The 20min behind the sub-dextran that awards high marks, the flow velocity of visible bulbar Conjunctiva Microcirculation obviously slows down.The blood flow form is the grain linear flow, and obvious granular sensation is arranged, and visible adularescent thrombosis sample material rolls and flows through blood vessel.After giving compound recipe notoginseng dripping pills preparation, visible microcirculatory grain flow process degree alleviates, and rare white thrombus sample material rolls at blood vessel.This experimental result has Video Document and photo to be card.
Discuss
This work has at first been observed the compound recipe notoginseng dripping pills to the dissolving of white mice clotting time, rats in vitro blood clot, the influence that the rat thrombus in vivo forms.The result proves that the compound recipe notoginseng dripping pills agent of various dose can prolong the clotting time of white mice, external blood clot to rat has tangible dissolution, and can alleviate the formation of rat thrombus in vivo, the agent of prompting compound recipe notoginseng dripping pills has good antithrombotic drug effect.This research proves that also the compound recipe notoginseng dripping pills agent of various dose also improves significantly to the hemodynamics of the rat of acute blood stasis and high blood viscosity model.Can reduce the whole blood viscosity and the erythrocyte rigidity index of acute blood stasis and high blood viscosity model, prompting compound recipe notoginseng dripping pills may reduce erythrocyte in microcirculatory incarceration and broken tendency by increasing erythrocytic deformation force.This research proves that also the agent of compound recipe notoginseng dripping pills can obviously reduce hematoblastic adhesion rate in the animal blood, helps to reduce the coagulability of blood, lowers thrombotic probability to a certain extent.Research has also been observed the compound recipe notoginseng dripping pills to the rat ridge oblique of high polysaccharide model and the influence of rabbit bulbar Conjunctiva Microcirculation, and the result shows the microcirculatory effect that has some improvement of compound recipe notoginseng dripping pills.
The stability of compound recipe notoginseng dripping pills of the present invention below is described by test.
One. the preliminarily stabilised test:
1. influence factor test: this product is through 2500-3000LX illumination, under high temperature (40 ℃, 60 ℃, 80 ℃) and the high humidity conditions such as (25 ℃ of temperature, relative humiditys 75% and 92.5%), detects in sampling in 0,1,3,5,10 day, and the result shows:
1) strong illumination does not all have obvious influence to the inherent quality and the outward appearance of compound recipe notoginseng dripping pills.
2) place 10 under the hot conditions, the result shows 40 ℃ of conditions placements 10 days, and sample appearance and inherent quality have no significant change.Place that sample begins fusing after 1 day for 60 ℃, other are all stablized.Under 80 ℃ of high temperature, drop pill melts, and melts liquid and begins to occur the small amount of degradation product in 10 days.
3) placed 10 days under the super-humid conditions, the sample surfaces moisture absorption tarnishes, and is the color of former medicine, and inherent quality does not have significant change.
2. accelerated test: sample is 40 ℃ of high temperature, and under relative humidity 75% condition, simulation listing packing was placed three months, and sampling is investigated respectively, with 0 day data and collection of illustrative plates relatively, every index is all up to specification.
3. room temperature reserved sample observing: three batches of imitation listing packing samples, place under the room temperature natural conditions to keep, respectively at investigating its every index in 1,3,6 month, and with 0 month data and collection of illustrative plates relatively, every index is all up to specification.
Claims (2)
1. Chinese medicine compound notoginseng dripping pills for the treatment of the oral administration of vascular lesions and hemorrhage thereof, it is to be prepared from by the Radix Notoginseng 250 of following weight portion proportioning, the Radix Astragali 80, Radix Salviae Miltiorrhizae 50, Radix Scrophulariae 80 and Macrogol 4000 or 6,000 360.
2. the preparation method of Chinese medicine compound notoginseng dripping pills according to claim 1 the steps include:
(1) Radix Notoginseng is pulverized, with 50-60% alcohol dipping twice, 4-6 days for the first time, 1-2 days for the second time, filter, merging filtrate is condensed into thick paste, oven dry is ground into fine powder, sieves, with the Radix Astragali, Radix Salviae Miltiorrhizae and Radix Scrophulariae with 50-60% alcohol heating reflux twice, 2-3 hour for the first time, 1-2 hour for the second time, filter, merging filtrate is spray dried to fine powder, with above-mentioned fine powder mixing, sieve, standby;
(2) taking polyethylene glycol 4000 or 6000 is heated to 80-90 ℃ and makes moltenly, and above-mentioned fine powder mixture is added, and stirs fusion, and is incubated 85 ℃;
(3) above-mentioned mixed liquor is poured in the drop pill device, 85 ℃ of water bath heat preservations splash in 5 ℃ the liquid paraffin, after the system of dripping finishes drop pill are continued to stay in the coolant, and it is fully cooled off, and take out, and inhale and remove surface liquid paraffin, are drying to obtain.
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| CN1322871C (en) * | 2003-11-07 | 2007-06-27 | 唐俊琪 | Preparation of compound pseudo-ginseng drop pellets for treating traumatologic disease |
| CN1297254C (en) * | 2004-11-26 | 2007-01-31 | 北京正大绿洲医药科技有限公司 | Drop pills containing bear gall and tendril-leaved fritillary bulb and preparation method thereof |
| CN1325042C (en) * | 2004-11-26 | 2007-07-11 | 北京正大绿洲医药科技有限公司 | Oral drop pills for treating bronchitis and preparation method thereof |
| CN1325043C (en) * | 2004-11-26 | 2007-07-11 | 北京正大绿洲医药科技有限公司 | Sweet wormwood oil drop pills and preparation method thereof |
| CN1307976C (en) * | 2004-11-30 | 2007-04-04 | 北京正大绿洲医药科技有限公司 | Thorax comforting drop pills for treating cardiopathy and preparation method thereof |
| CN1297255C (en) * | 2004-11-30 | 2007-01-31 | 北京正大绿洲医药科技有限公司 | Dripping pills for treating high blood fat and its preparing method |
| CN1297256C (en) * | 2004-11-30 | 2007-01-31 | 北京正大绿洲医药科技有限公司 | Oral drop pills for treating coronary disease and preparation method thereof |
| CN102895559A (en) * | 2012-10-30 | 2013-01-30 | 唐雯 | Chinese medicinal preparation for treating central serous chorioretinopathy |
| CN104666816A (en) * | 2015-02-12 | 2015-06-03 | 张宏国 | Traditional Chinese medicine preparation for treating retinal arterial obstruction |
| CN106994150A (en) * | 2017-04-22 | 2017-08-01 | 张挺 | A kind of Chinese medicine dripping pills for treating blood vessel venereal disease and preparation method thereof |
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Free format text: COMMON LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2008.9.5 TO 2011.9.4; CHANGE OF CONTRACT Name of requester: GUANGDONG SHUNFENG PHARMACEUTICAL CO., LTD. Effective date: 20081024 |
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| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20030820 Assignee: GUANGZHOU WEISIBAO PHARMACEUTICAL Co.,Ltd. Assignor: Huang Haibo Contract record no.: 2014440000020 Denomination of invention: Compound Chinese medicine notoginseng dripping pills and its prepn process Granted publication date: 20060524 License type: Common License Record date: 20140122 |
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Effective date of registration: 20170706 Address after: 510300, 704, building 211, 157 southeast of grand Haizhuqu District, Xingang West Road, Guangzhou, Guangdong Co-patentee after: GUANGZHOU WEISIBAO PHARMACEUTICAL Co.,Ltd. Patentee after: Huang Haibo Address before: West Lake road Guangzhou city Guangdong province 510030 Silver Lake No. 38 building 11H Patentee before: Huang Haibo |
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Granted publication date: 20060524 |
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Addressee: Patent of Guangzhou WeiSiBao Pharmaceutical Co.,Ltd. The person in charge Document name: Notice of expiration and termination of patent right |
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| DD01 | Delivery of document by public notice |