CN104116812A - Pharmaceutical composition for treating internal haemorrhage and application thereof - Google Patents
Pharmaceutical composition for treating internal haemorrhage and application thereof Download PDFInfo
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- CN104116812A CN104116812A CN201410398046.3A CN201410398046A CN104116812A CN 104116812 A CN104116812 A CN 104116812A CN 201410398046 A CN201410398046 A CN 201410398046A CN 104116812 A CN104116812 A CN 104116812A
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- folium caryophylli
- ethanol extract
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- 208000032843 Hemorrhage Diseases 0.000 title claims abstract description 44
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
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- 239000000469 ethanolic extract Substances 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
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- HBGOLJKPSFNJSD-UHFFFAOYSA-N Etamsylate Chemical compound CC[NH2+]CC.OC1=CC=C(O)C(S([O-])(=O)=O)=C1 HBGOLJKPSFNJSD-UHFFFAOYSA-N 0.000 description 1
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- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a pharmaceutical composition for treating internal haemorrhage and application thereof. The composition is prepared from active ingredients and auxiliary materials, wherein the active ingredients are pilose leptodermis leaf alcohol extracts. The pharmaceutical composition is obvious in hemostatic and coagulating effects, can be used for severe refractory functional uterine bleeding, alimentary tract hemorrhage and internal haemorrhage diseases and also can be used for treating various hemorrhage syndromes which are not obvious in effects of conventional hemostatics.
Description
Technical field
The invention belongs to medical technical field, in particular to a kind of medical composition and its use for the treatment of internal hemorrhage.
Background technology
Blood is the material that body weight for humans is wanted, and all hemorrhage diseases, as effectively hemostasis not in time, cause blood consume, and cause body weak, and even threat to life, therefore the application of hemorrhage has great importance.Hemorrhage two kinds of external haemorrhage and the internal hemorrhages that are divided into.Blood flows to body epigenesist from wound and is called external haemorrhage, is common in the wound of lancinating, stabs, gunshot wound and spreading wound etc.If skin does not have wound, blood is flow in tissue, internal organs or body cavity by the blood vessel breaking, and is called internal hemorrhage.The reason that causes internal hemorrhage for complicated, is processed also more difficultly far beyond external haemorrhage, needs to go hospital therapy more.Blood is stopped, and is the main purpose of the traumatic external haemorrhage for the treatment of.According to external haemorrhage kind difference, Hemostasis is also different.Doing clinically multiplex is compressing and hemostasis with packs method, but this Hemostasis is not easily effectively.
In hemostatic agent, there is several formulations perhaps, such as etamsylate, vitamin K, carbazochrome salicylate, GONGXUENING etc., these medicaments are conventional therapy medication or auxiliary treatment medication, versatility is stronger, but drug effect is obvious not.The course for the treatment of, longer curative effect was slower, in the time that conditions of patients is light, can obtain therapeutic effect, in the time that conditions of patients is serious, was difficult for obtaining the effect of basic treatment.Some Western medicine being synthesized by chemical substance has certain therapeutic effect, but Western medicine often toxic and side effects is larger, can stimulate stomach discomfort, and price is more expensive.
Summary of the invention
In view of the deficiencies in the prior art, the object of the present invention is to provide a kind of haemostatic medicament for the treatment of internal hemorrhage.Hemostasis, the blood coagulation enhancing effect of this medicine are remarkable, can be used for the internal hemorrhage such as metrorrhagia, digestive tract hemorrhage disease.
The object of the present invention is achieved like this:
Treat a pharmaceutical composition for internal hemorrhage, be prepared from by active component and adjuvant, described active component is Folium Caryophylli ethanol extract.The ethanol extraction that preferably described Folium Caryophylli ethanol extract is Folium Caryophylli.Wherein, Folium Caryophylli is selected the leaf of Rubiaceae hair Flos syringae persicae Leptodermis pilosa (Franch.) Diels; Can be fresh goods, can be also wet product.
Further, the pharmaceutical composition of described treatment internal hemorrhage, Folium Caryophylli ethanol extract wherein can be prepared from as follows: Folium Caryophylli is placed in to extraction element, successively doubly measure the 85-90%(v/v of (v/w) with 8-15) ethanol, 60-65%(v/v) alcohol reflux, merge extractive liquid,, filters, and reclaims ethanol and continues to be condensed into thick paste, dry, obtain Folium Caryophylli ethanol extract.
It should be noted that, the pharmaceutical composition for the treatment of internal hemorrhage of the present invention, it is preferably prepared into oral formulations.Described oral formulations comprises oral liquid, tablet, capsule, granule.According to the common process of formulation art, those skilled in the art is easy to adjuvant available on Folium Caryophylli ethanol extract and pharmaceutics to be prepared into conventional solid orally ingestible, as granule, tablet, capsule.Wherein, on pharmaceutics, available adjuvant comprises filler, disintegrating agent, binding agent, correctives, lubricant etc.
The inventor finds after by a large amount of experimental studies, and Folium Caryophylli ethanol extract all can obviously shorten mice plasma recalcification time, clotting time and bleeding time, has significant hemostasis, blood coagulation enhancing effect; It may be by the multiple thrombin of activation endogenous and exogenous cruor pathway, promote that thrombinogen and thromboplastin generate, accelerating fibers albumen is synthetic, thereby reach the biological activity of hemostasis, coagulant.Based on above result of study, the present invention also provides a kind of pharmaceutical applications, that is: the purposes of Folium Caryophylli ethanol extract in the oral drugs of preparation treatment internal hemorrhage.
Compared with prior art, pharmaceutical composition of the present invention stops blooding, blood coagulation enhancing effect is remarkable, can be used for the internal hemorrhage diseases such as serious obstinate dysfunctional uterine hemorrhage, digestive tract hemorrhage, and can be used for treating the various hemorrhages of conventional hemorrhage DeGrain.
Detailed description of the invention
Be below Preparation Example and the effect test example of Folium Caryophylli ethanol extract of the present invention, the present invention will be further explained, but this not means that protection scope of the present invention is subject to the restriction of following embodiment.
The preparation of embodiment 1 Folium Caryophylli ethanol extract
Folium Caryophylli dry product 2kg, puts in round-bottomed flask, is 90%(v/v respectively by 20L concentration) ethanol and 65%(v/v) the each reflux, extract, of ethanol 2 times, each 4h, inclines and alcohol extract.Merge 4 times extracting solution, filter, reclaim ethanol and continue to be condensed into thick paste, 70 DEG C of drying under reduced pressure, are ground into fine powder, cross 100 mesh sieves, obtain Folium Caryophylli ethanol extract.
The preparation of embodiment 2 Folium Caryophylli ethanol extract
Folium Caryophylli dry product 1kg, puts in round-bottomed flask, is 85%(v/v respectively by 13L concentration) ethanol and 60%(v/v) the each reflux, extract, of ethanol 2 times, each 4h, inclines and alcohol extract.Merge 4 times extracting solution, filter, reclaim ethanol and continue to be condensed into thick paste, 70 DEG C of drying under reduced pressure, are ground into fine powder, cross 100 mesh sieves, obtain Folium Caryophylli ethanol extract.
Embodiment 3 mice plasma recalcification time experiments
36 of SPF level NIH kind mices, weight 18-22g, be divided at random 3 groups, male and female half and half, be respectively that matched group (15mL/kg normal saline), Folium Caryophylli ethanol extract are low, high dose group (give Folium Caryophylli ethanol extract prepared by the embodiment of the present invention 1, dosage is respectively 65,130mg/kg), gastric infusion, 1 time/d, 7d continuously.1h after administration in the 7th day, wins eyeball and gets blood 1mL, puts into the centrifuge tube that is added with liquor sodii citratis, and with centrifugal 10 min of 3000r/min, separated plasma is for subsequent use.Get upper plasma 0.1mL in test tube, put into 37 DEG C of water-bath incubation 2min, then add 0.25mol/L calcium chloride solution 0.1mL; After mixing, put into again 37 DEG C of water-baths, start timing simultaneously.After 1min every slowly tilt test tube 1 time of 15s.From adding, calcium chloride solution to fibrin solidifies record, the motionless required time of liquid level, is blood plasma recalcification time (PRT).
PRT LVFS=(matched group PRT-administration group PRT)/matched group PRT × 100%
Folium Caryophylli ethanol extract the results are shown in Table 1 to the impact of mice PRT.Result demonstration, with matched group comparison, medicine is low, high dose group all can significantly shorten PRT(
p< 0.01), and shorten with the increase of dosage, this is indicating that Folium Caryophylli ethanol extract of the present invention has hemostasis, blood coagulation enhancing effect.
The comparison of the each group of table 1 mice plasma recalcification time
| Group | Sample size | PRT（s） | PRT LVFS (%) |
| Matched group | 12 | 98.0±13.1 | - |
| Medicine high dose group | 12 | 64.9±9.6 ## | 33.8 |
| Medicine low dose group | 12 | 73.2±10.5 ## | 25.3 |
With matched group comparison,
# p< 0.05,
## p< 0.01.
Embodiment 4 clotting time of mice experiments
36 of SPF level NIH kind mices, weight 18-22g, be divided at random 3 groups, male and female half and half, be respectively that matched group (15mL/kg normal saline), Folium Caryophylli ethanol extract are low, high dose group (give Folium Caryophylli ethanol extract prepared by the embodiment of the present invention 1, dosage is respectively 65,130mg/kg), gastric infusion, 1 time/d, 7d continuously.After the 7th day administration 30min, carry out as follows: 1. capillary glass-tube method: insert mice endocanthion eyeball rear vein beard with capillary glass-tube and get blood, till reaching 5cm blood post.Every 30s little section of the capillary glass-tube one that fractures, check and have or not blood clotting silk to occur; Record is taken a blood sample to and is occurred the time of blood clotting silk from capillary glass-tube, is clotting time CT1.2. slide method: win rapidly a branch hole ball with the curved tweezer of ophthalmology, have blood to flow out; Bleed for each one in microscope slide two ends, drop of blood diameter is about 5mm, uses immediately manual time-keeping; Provoke once gently inwards from drop of blood edge with clean pin every 30s, and observation has or not the blood streak to provoke; Start to only provoking the blood streak from blood sampling, between institute lasts, be clotting time CT2; Another is bled and reviews for last.
CT LVFS=(matched group CT-administration group CT)/matched group CT × 100%
Folium Caryophylli ethanol extract on the impact of clotting time of mice the results are shown in Table 2, table 3.Result demonstration, with matched group comparison, medicine is low, high dose group all can significantly shorten PRT(
p< 0.05 or
p< 0.01), and shorten with the increase of dosage, this is also indicating that Folium Caryophylli ethanol extract of the present invention has hemostasis, blood coagulation enhancing effect.
The comparison of the each group of table 2 mice capillary glass-tube method clotting time
| Group | Sample size | CT1（s） | CT1 LVFS (%) |
| Matched group | 12 | 159.6±22.5 | - |
| Medicine high dose group | 12 | ?105.8±13.7 ## | 33.7 |
| Medicine low dose group | 12 | 134.7±16.3 # | 15.6 |
With matched group comparison,
# p< 0.05,
## p< 0.01.
The comparison of the each group of table 3 mice slide method clotting time
| Group | Sample size | CT2（s） | CT2 LVFS (%) |
| Matched group | 12 | 251.7±24.4 | - |
| Medicine high dose group | 12 | 179.0±16.8 ## | 28.9 |
| Medicine low dose group | 12 | 203.2±19.5 ## | 19.3 |
With matched group comparison,
# p< 0.05,
## p< 0.01.
Embodiment 5 mice bleeding time experiment
36 of SPF level NIH kind mices, weight 18-22g, be divided at random 3 groups, male and female half and half, be respectively that matched group (15mL/kg normal saline), Folium Caryophylli ethanol extract are low, high dose group (give Folium Caryophylli ethanol extract prepared by the embodiment of the present invention 1, dosage is respectively 65,130mg/kg), gastric infusion, 1 time/d, 7d continuously.After the 7th day administration 30min, cut off the about 3mm of Mouse Tail-tip, timing immediately, treats that blood overflows voluntarily; Every filter paper gentle aspiration drop of blood for 30s, taking manually form wound surface to stopped bleeding through the time as the bleeding time, record the bleeding time (BT).
BT LVFS=(matched group BT-administration group BT)/matched group BT × 100%
Folium Caryophylli ethanol extract the results are shown in Table 4 to the impact in mice bleeding time.Result show, with matched group comparison, medicine is low, high dose group all can significantly shorten docking the bleeding time (
p< 0.05 or
p< 0.01), and the bleeding time shorten with the increase of dosage, this is also indicating that Folium Caryophylli ethanol extract of the present invention has hemostasis, blood coagulation enhancing effect.
The mice bleeding time comparison of the each group of table 4
| Group | Sample size | BT（s） | BT LVFS (%) |
| Matched group | 12 | 662.5±70.5 | - |
| Medicine high dose group | 12 | 374.0±33.6 ## | 43.5 |
| Medicine low dose group | 12 | 583.7±48.6 # | 11.9 |
With matched group comparison,
# p< 0.05,
## p< 0.01.
Claims (6)
1. treat a pharmaceutical composition for internal hemorrhage, be prepared from by active component and adjuvant, it is characterized in that: described active component is Folium Caryophylli ethanol extract.
2. the pharmaceutical composition for the treatment of according to claim 1 internal hemorrhage, is characterized in that: the ethanol extraction that described Folium Caryophylli ethanol extract is Folium Caryophylli.
3. according to the pharmaceutical composition for the treatment of internal hemorrhage described in claim 1 or 2, it is characterized in that: described Folium Caryophylli ethanol extract is prepared from as follows: Folium Caryophylli is placed in to extraction element, successively doubly measure the 85-90%(v/v of (v/w) with 8-15) ethanol, 60-65%(v/v) alcohol reflux, merge extractive liquid,, filter, reclaim ethanol and continue to be condensed into thick paste, dry, obtain Folium Caryophylli ethanol extract.
4. according to the pharmaceutical composition for the treatment of internal hemorrhage described in claim 1 or 2, it is characterized in that: described pharmaceutical composition is oral formulations.
5. the pharmaceutical composition for the treatment of according to claim 4 internal hemorrhage, is characterized in that: described oral formulations comprises oral liquid, tablet, capsule, granule.
6. the purposes of Folium Caryophylli ethanol extract in the oral drugs of preparation treatment internal hemorrhage.
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| CN109432175A (en) * | 2018-12-27 | 2019-03-08 | 大理大学 | The preparation method and antimalarial purposes of river Yunnan open country Flos Caryophylli extract and its pharmaceutical composition |
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| WO2009125017A2 (en) * | 2008-04-11 | 2009-10-15 | Institut De Recherche Pour Le Développement (Ird) | Process for the extraction of mangiferin and isomangiferin |
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2014
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