CN105832922A - Application of woman dysmenorrhea granules to medicines for improving blood rheology - Google Patents
Application of woman dysmenorrhea granules to medicines for improving blood rheology Download PDFInfo
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- CN105832922A CN105832922A CN201610401511.3A CN201610401511A CN105832922A CN 105832922 A CN105832922 A CN 105832922A CN 201610401511 A CN201610401511 A CN 201610401511A CN 105832922 A CN105832922 A CN 105832922A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/66—Papaveraceae (Poppy family), e.g. bloodroot
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/24—Mucus; Mucous glands; Bursa; Synovial fluid; Arthral fluid; Excreta; Spinal fluid
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
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Abstract
The invention provides application of woman dysmenorrhea granules to medicines for improving blood rheology and relates to a new usage of the woman dysmenorrhea granules. The invention provides the application of the woman dysmenorrhea granules to the medicines for improving the blood rheology. Furthermore, the woman dysmenorrhea granules can be applied to medicines capable of promoting blood circulation and removing blood stasis. The woman dysmenorrhea granules can obviously inhibit platelet aggregation induced by ADP and collagen; after the woman dysmenorrhea granules are intravenously injected, the formation of rat common carotid artery-vein bypass experimental thrombosis is obviously inhibited.
Description
Technical field
The present invention relates to the new application of dysmenorrhes granule, be specifically related to dysmenorrhes granule and improving hemorheology medicine
Application in thing.
Background technology
Dysmenorrhes granule is made up of Rhizoma Corydalis (vinegar system), Oletum Trogopterori (vinegar-fried), Radix Salviae Miltiorrhizae, Pollen Typhae (charcoal) four taste Chinese medicine,
Control blood, regulating menstruation, effect of pain relieving.For blood stagnation, lower abdominal distention pain, abdominal pain in menstruation.
Hemorheology is in macroscopic view, microcosmic, submicroscopic level, the research cell component of blood and the deformation of blood plasma and
Flow performance, and the rheological behavior of the blood vessel structure directly contacted with blood.Through modern study Patients with Blood Stasis Syndrome hemorheology
Property all shows as sticking, dense, solidifying, poly-；There were significant differences with normal women for the hemorheological property of dysmenorrhea patient, and the height of dysmenorrhea patient is cut
Rate and undercut rate whole blood viscosity raise the most extremely.In terms of modern hemodynamic angle, blood is equivalent to blood circulation of human body,
The change of the flowing of blood and deformation, i.e. rheological characteristic, is blood circulation and the occurrence cause of microcirculation disturbance and basis.
Hemorheologic agent is to prevention and to treat some disease significant, the clinical symptoms of numerous disease and blood
Liquid stream degeneration is abnormal relevant, and generation, the development of disease are played an important role by Human Hemorrheology abnormal change, improve blood
The parameter of fluid rheology, it will help the mitigation of disease and improvement, therefore, from the work of hemorheology angle Study of Traditional Chinese Medicine medicine
By principle, finding and paying attention to intervening the Chinese medicine of hemorheology change is that the difficult problem that overcome is presently required.
Summary of the invention
It is an object of the invention to for described above, it is provided that a kind of dysmenorrhes granule is in improving hemorheologic agent
Application.
It is an object of the invention to be achieved by the following technical programs.
The dysmenorrhes granule of the present invention application in improving hemorheologic agent.
Further, dysmenorrhes granule of the present invention can apply to activating blood and removing stasis drug.
The drug effect basis of dysmenorrhes granule therapy dysmenorrhea is relevant with by improving dysmenorrhea hemorheology in patients.Women's pain
Effective component in red sage in granule prescription is divided into water solublity and alcohol-soluble two parts.Water solublity danshensu not only can restrain cell
The synthesis of endogenous cholesterol, removing O2Reduce H2O2Generation, block free radical generation, prevent lipoprotein oxidation, Er Qieyou
Blood circulation and channel invigorating, tinea of dispelling nourish blood, remove power free radical, dredging microcirculation, anticoagulant, antithrombotic effect.Oletum Trogopterori has substantially lives
The effect of blood blood stasis dispelling.Oletum Trogopterori water extract is external can substantially be suppressed by the Platelet Aggregation in Rabbits of the induction such as ADP, collagen, and it presses down
Make of relevant to dosage.Rats by intraperitoneal injection also can substantially suppress by ADP, collagen-induced platelet aggregation.Intravenous injection
Rat carotid artery-venous bypass experimental vein thrombosis there is obvious inhibitory action.This is used for making for dysmenorrhes granule
Material base is provided for improving hemorheologic agent.
Detailed description of the invention
In order to be best understood from the essence of the present invention below by with the pharmacodynamic experiment of the present invention for illustrating that it is improving
Effect in terms of hemorheology.
One, dysmenorrhes granule improves hemorheology index effect experiment.
1 materials and methods.
1. 1 animal health female sd inbred rats 50, weight (300 ± 20) g, Jiangsu Province's Experimental Animal Center carry
Supply.
1. 2 experimental apparatus and reagent.
1.2.1 reagent: dysmenorrhes granule (capital, Shandong drive hall traditional Chinese medicines traditional Chinese medicines company limited), adrenalin hydrochloride
(adrenaline) injection: 10ug.ml-1, Tianjin KingYork Amino Acid Co., Ltd., lot number: 20130201；Thrombin time
(thrombin time, TT) reagent, activated partial thromboplastin time (activated partial thromboplastin
Time, APTT) reagent, prothrombin time (prothrombin time, PT) reagent and Fibrinogen (fibrinogen, F
Ib) reagent, diligent generation Supreme Being's Scientific Instruments Corporation in Beijing；Adenosine diphosphate (ADP) (adenosine diphosphate, ADP), lot number:
13052004, Shanghai Inst. of Biochemistry, Chinese Academy of Sciences.
1.2.2 key instrument: LG-R-80B type blood viscosity instrument, ALG-PABER-I platelet aggregation thrombin is analyzed
Instrument, LBY-BX2 red blood cell deformation instrument are purchased from Beijing Zhong Qinshidi scientific instrument company limited；TGL-16G A frozen centrifugation
Machine, Anting Scientific Instrument Factory, Shanghai；The multi-functional high speed centrifugal machine for minim of K2015R type, centurion company of Britain.
1. 3 experiment packet and medication: rat is numbered, is randomly divided into 5 groups, often group 10.It is blank right to be followed successively by
According to concentration group (Z), dysmenorrhes in group (K), model group (M), dysmenorrhes granule low concentration group (D), dysmenorrhes granule
Grain high concentration group (G).Latter 3 groups is administration group, respectively with 0.1g/kg, 0.15g/ kg, 0.2g/kg (patent medicine quality/rat body
Dosage gavage heavily), matched group, model group give normal saline.1 time/d, continuous 7d, and replicated " blood stasis " in the 7th day
Model, after fasting 12h, secondary morning takes blood censorship.
1. after gavage the 7th day of 4 " blood stasis " model copy method, to rat skin lower injection epinephrine 0.008mL/kg
(except blank group), totally 2 times, is spaced 4h.2h after the 1st injection, immerses 4 DEG C of frozen water 5min, then fasting by rat,
Dispose next day and can form " blood stasis " model.
1. 5 observation index and detection method.
1.5.1 packed cell volume: taking heparin sodium anticoagulation is appropriate, and 15000*g is centrifuged 5min, surveys with micro-capillary tubes method
Determine packed cell volume (hematocrit).
1.5.2 whole blood viscosity and plasma viscosity: with cone-plate formula rotary viscosity design determining rat whole blood viscosity.Taking heparin resists
Solidifying 0.8mL whole blood adds in the sample cell of blood viscosity meter, glues in 37 DEG C of whole bloods measured under shear rate 200,100 and 1s-1
Degree, and calculate erythrocyte aggregation index (erythrocyte aggregation index, EA I), i.e. EAI=G1/G100, its
Middle G1 is the whole blood viscosity under shear rate 1s-1, and G100 is the whole blood viscosity under shear rate 100s-1.Take 2mL heparin anti-coagulating,
3000*g is centrifuged 15min, takes 0.8mL blood plasma and measures plasma viscosity in 37 DEG C.
1.5.3 plasma fibrinogen (FgP): take EDTA-2Na or sodium citrate anticoagulant blood plasma 0.3ml, add
0.45mol/L CaCl:10ml, 37 DEG C of water-baths 60 minutes, with glass rod roll out fiber egg from, distilled water washes away attachment protein, extracts
Moisture, adds normal saline 0.3ml in grumeleuse, add protein standard liquid 0.3ml in standard pipe, and blank tube adds distilled water 0.3ml, respectively adds
Biuret reagent 2.0m1, puts 56 DEG C of water-baths, fully mixes once when 5 minutes, within 20 minutes, takes out, is cooled to room temperature.540nm wavelength,
10mm optical path, 722 type spectrophotometric colo, result calculates or looks into standard curve.
1.5.4 platelet aggregation (A): taking sodium citrate anticoagulation 2mL, 800*g is centrifuged 10min, prepares rich platelet blood
Slurry；It is centrifuged 10min with 2500*g again, prepares platelet poor plasma, regulate Platelet Density about 2.5*108mL-1, with final concentration
5umol/L ADP is platelet aggregation derivant, uses turbidimetry to measure PAR in 37 DEG C.
1.6 experimental datas represent with x ± s, use SPSS 18.0 software kit to carry out statistical analysis.Multiple-group analysis uses single
Analysis of variance, two compare employing t inspection.
2 experimental results.
Change " blood stasis " model group rats of 2.1 " blood stasis " rat model hemorheological indexes and blank group
Relatively, every hemorheology index is all substantially abnormal (P < 0.05), presents significantly " blood stasis " card of " dense, glutinous, solidifying, poly-"
Feature.
The all impacts on " blood stasis " hemorheology of rat indices of the 2.2 high, normal, basic dosage of dysmenorrhes granule.
2.2.1 the impact on the index packed cell volume of " dense ", is shown in Table 1.
Dysmenorrhes granule basic, normal, high dosage group all has the effect of improvement " blood stasis " Rat Erythrocytes hematocrit, all can be substantially
Reducing HCT counting, and middle dosage and high dose group no significant difference, the two overstocks aspect and compares low dose group improving erythrocyte
There is notable difference.
Table 1 dysmenorrhes granule is on " blood stasis " Rat Erythrocytes hematocrit and the impact of plasma fibrinogen.
Note: compared with blank group, * * P < 0.01；Compared with model group, △ △ P < 0.01.
2.2.2 index whole blood viscosity and the impact of erythrocyte aggregation index on " sticking ", is shown in Table 2.
Table 2 dysmenorrhes granule is on " blood stasis " rat whole blood viscosity and the impact of erythrocyte aggregation index.
Note: * P < 0.05, * * P < 0.01 compared with blank group；△ △ P < 0.01 compared with model group.Dysmenorrhes
Granule woman to whole blood viscosity slightly improvement result, but improves poor effect at low dosage.At middle dosage and high dose, all have substantially
Reduce the blood viscosity cutting rate 3/S, 100/S, 200/S.
2.2.3 the impact on the index plasma fibrinogen of " coagulating ", is shown in Table 1.
Equal " blood stasis " the rat plasma fibrinogen content that can reduce of the high, medium and low dosage of dysmenorrhes granule, middle and high dose
Amount group is improved effect no significant difference and is substantially better than low dosage administration group (P < 0.01).
2.2.4 the impact on the index platelet aggregation of " gathering ", is shown in Table 3.
The impact on " blood stasis " rat platelet aggregation of the table 3 dysmenorrhes granule.
Note: * * P < 0.01 compared with blank group；△ △ P < 0. 01 compared with model group.
Dysmenorrhes granule high, medium and low dosage group all can substantially suppress rat's blood stasis model platelet aggregation collection, and between three
No significant difference.
From above-mentioned experiment, the every hemorheology index of acute blood-stasis model group rat compares with normal control to be had relatively
Significant change, shows that whole blood viscosity, erythrocyte overstock value significantly raised, and the platelet aggregation time shortens.The present invention relates to medicine
Thing dysmenorrhes granule can be obviously improved the every hemorheology index of blood stasis model rat, is allowed to recover normal, shows woman
Female's Tongjing granule has obvious the effect ofactivating blood circulation to dissipate blood stasis.
Two, dysmenorrhes granule toxicological experiment.
1. test material.
1.1 animals: healthy Kunming mouse, are supplied by Institute of Experimental Animals, Chinese Academy of Medical Sciences.
1.2 samples (tested material): dysmenorrhes granule, are provided by Shandong Jingyutang Traditional Chinese Medicine Co., Ltd..
2. test method and result.
The mensuration of maximum tolerated dose (MTD):
Take body weight 19-21g healthy mice 20, female, sample with Cmax (1.2g/ml) maximum volume (0.8ml/g),
In 24 hours, gavage 3 times respectively, observe once, observe seven days every day.Within 2nd, 5,8 days, body is respectively claimed before being administered and after being administered
Weight the most once, the results are shown in Table 4 and table 5.
Table 4 reaction of animals situation.
Table 5 the weight of animals change (X ± SD).
From table 4 and table 5 observed result, whole mices have no untoward reaction and death, and body weight increases.
3. conclusion.
This product, with 48.0g crude drug/Kg dosage, gave mouse stomach 3 times in 24 hours, 360 times of suitable people's daily dose,
Have no untoward reaction and death, show that this product toxicity is relatively low.
Claims (3)
1. dysmenorrhes granule application in improving hemorheologic agent.
The dysmenorrhes granule the most according to claim 1 application in improving hemorheologic agent, it is characterised in that:
Described dysmenorrhes granule is applied to activating blood and removing stasis drug.
The dysmenorrhes granule the most according to claim 1 application in improving hemorheologic agent, it is characterised in that:
The dosage of described dysmenorrhes granule is: dysmenorrhes granular mass/body weight=0.1-0.2g/kg.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610401511.3A CN105832922A (en) | 2016-06-10 | 2016-06-10 | Application of woman dysmenorrhea granules to medicines for improving blood rheology |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610401511.3A CN105832922A (en) | 2016-06-10 | 2016-06-10 | Application of woman dysmenorrhea granules to medicines for improving blood rheology |
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| CN105832922A true CN105832922A (en) | 2016-08-10 |
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| CN201610401511.3A Pending CN105832922A (en) | 2016-06-10 | 2016-06-10 | Application of woman dysmenorrhea granules to medicines for improving blood rheology |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1548125A (en) * | 2003-05-11 | 2004-11-24 | 山东绿因药业有限公司 | Dysmenorrhea treating granule and its prepn process |
| CN104435435A (en) * | 2014-12-16 | 2015-03-25 | 山东京御堂国药有限公司 | Traditional Chinese medicine granule for treating dysmenorrheal of women and preparation method of traditional Chinese medicine granule |
| CN104510854A (en) * | 2014-12-16 | 2015-04-15 | 山东京御堂国药有限公司 | Traditional Chinese medicinal composition for treating dysmenorrhea of women and application of traditional Chinese medicinal composition |
| CN104510853A (en) * | 2014-12-16 | 2015-04-15 | 山东京御堂国药有限公司 | Traditional Chinese medicinal effective part composition for treating dysmenorrhea of women and application of traditional Chinese medicinal effective part composition |
-
2016
- 2016-06-10 CN CN201610401511.3A patent/CN105832922A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1548125A (en) * | 2003-05-11 | 2004-11-24 | 山东绿因药业有限公司 | Dysmenorrhea treating granule and its prepn process |
| CN104435435A (en) * | 2014-12-16 | 2015-03-25 | 山东京御堂国药有限公司 | Traditional Chinese medicine granule for treating dysmenorrheal of women and preparation method of traditional Chinese medicine granule |
| CN104510854A (en) * | 2014-12-16 | 2015-04-15 | 山东京御堂国药有限公司 | Traditional Chinese medicinal composition for treating dysmenorrhea of women and application of traditional Chinese medicinal composition |
| CN104510853A (en) * | 2014-12-16 | 2015-04-15 | 山东京御堂国药有限公司 | Traditional Chinese medicinal effective part composition for treating dysmenorrhea of women and application of traditional Chinese medicinal effective part composition |
Non-Patent Citations (2)
| Title |
|---|
| 刘福强等主编: "《医师案头用药参考 中成药化学药》", 31 March 2012, 中国中医药出版社 * |
| 罗颂平主编: "《中国百年百名中医临床专家丛书 妇科专家卷》", 30 November 2012, 中国中医药出版社 * |
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