CN101862392B - New pharmaceutical application of cordate houttuynia in thrombus prevention - Google Patents
New pharmaceutical application of cordate houttuynia in thrombus prevention Download PDFInfo
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- CN101862392B CN101862392B CN2009102373481A CN200910237348A CN101862392B CN 101862392 B CN101862392 B CN 101862392B CN 2009102373481 A CN2009102373481 A CN 2009102373481A CN 200910237348 A CN200910237348 A CN 200910237348A CN 101862392 B CN101862392 B CN 101862392B
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- cordate houttuynia
- herba houttuyniae
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Abstract
The invention belongs to the field of medicaments, relates to new pharmaceutical application of cordate houttuynia in thrombus prevention, and aims to provide the new application of the cordate houttuynia in preparation of the medicaments for preventing and/or curing thrombus and antithrombotic medicaments. Cordate houttuynia active ingredients are prepared by distilling fresh or dry cordate houttuynia, decocting the fresh or dry cordate houttuynia with water and extracting the fresh or dry cordate houttuynia with an organic solvent or volatile oil. Animal tests show that the cordate houttuynia has the obvious effects of resisting the thrombus and suppressing blood platelet consumption and leucocyte consumption caused by the thrombus. The effects are not reported and applied in conventional research and clinical use of the cordate houttuynia, so the new application has uniqueness and novelty. The cordate houttuynia has the advantages of broad resource, simple and convenient extraction method and the capability of being prepared into various formulations; and the thromboembolic disease is the most common disease and has great requirement on the clinical use of medicaments; and thus the pharmaceutical application has high practicability and broad prospect in the application of preventing and/or curing the thrombus.
Description
One, technical field
The invention belongs to field of medicaments.
Two, background technology
Herba Houttuyniae is a saururaceae plant houttuynia cordata, another name Herba Houttuyniae, hog snout arch (hog snout hole), Rhizoma Rohdeae Japonicae, the folding basal part of the ear, Herba Tripterospermi, smelly raw meat grass.All both edible is also pharmaceutically acceptable for Herba Houttuyniae herb (aerial parts and under ground portion).When medicinal, both available bright article, also available dry product.Herba Houttuyniae has heat-clearing and toxic substances removing, eliminating carbuncle evacuation of pus, the function of inducing diuresis for treating stranguria syndrome.Be used for the lung abscess vomiting pus, the expectorant dyspnea of heat type is coughed, hematodiarrhoea, and pyretic stranguria, carbuncle sore tumefacting virus, like pulmonary abscess, phlegm-heat cough, oedema due to nephritis, urinary tract infection, carbuncle furuncle.Clinically, Herba Houttuyniae is made into external, oral and injection application.
1. Herba Houttuyniae many-sided drug action that has been in the news, but do not see the research report that antithrombotic or anticoagulation aspect are arranged.
Research proof Herba Houttuyniae in the past has following effect: the effect of (1) resisting pathogenic microbes: can suppress staphylococcus aureus, hemophilus influenza, Diplococcus pneumoniae growth; (2) diuresis can increase secretion of urine, can be used for the puckery pain of pollakiuria of urinary tract infection; (3) enhance immunity effect: can improve the leukocytic phagocytosis of chronic tracheitis patient; (4) anti-allergic effects: can improve animal allergic rhinitis symptom.But do not see record of relevant Herba Houttuyniae antithrombotic or anticoagulant document or formal disclosed research report.
2. the Herba Houttuyniae clinical practice is extensive, but does not see that it is in the application of thrombotic disease aspect preventing and treating
Herba Houttuyniae is extensive in clinical practice, both can use separately, also can form compound recipe with other drug and use, and existing injection also has oral, external preparation use.Its purposes is used for treating diseases such as respiratory tract infection that virus or antibacterial cause, urinary system infection, pharyngitis, tonsillitis, nephritis more.Houttuynia cordata injection is used very extensive.According to the national standard of Herba Houttuyniae injectio and the description of manufacturer, [function cures mainly] of Herba Houttuyniae injectio is heat clearing away, detoxifcation, dampness removing.Range of application is: lung abscess, phlegm-heat cough, leucorrhea, urinary tract infection, carbuncle furuncle.[function cures mainly] of Herba Houttuyniae compound preparation such as FUFANG YUXINGCAO PIAN (Herba Houttuyniae, Radix Scutellariae, Radix Isatidis, Fructus Forsythiae, Flos Lonicerae) is heat-clearing and toxic substances removing, is used for acute inflammation of the throat, acute tonsillitis due to the affection due to external wind and heat, and disease is seen red swelling of the pharynx, pharyngalgia; Acute pharyngitis, acute tonsillitis are seen above-mentioned patient.[function cures mainly] of cordate houttuynia eye drops is heat clearing away, detoxifcation, dampness removing.Be used for wind heat epidemic disease poison, acute conjunctivitis, epidemic keratoconjunctivitis (acute catarrhal conjunctivitis, epidemic keratoconjunctivitis).So far, do not see that Herba Houttuyniae is the compound recipe of main component is used to prevent and treat thrombosis or blood coagulation with the related preparations of any route of administration clinical practice report separately or with the Herba Houttuyniae.
Three, summary of the invention
In order to make full use of the Herba Houttuyniae resource, enlarge the clinical practice of Herba Houttuyniae, the inventor gives behind the rat suppository model inhibitory action research to thrombosis through Herba Houttuyniae; The influence of the platelet consumption that Herba Houttuyniae gives thrombosis to be caused behind the rat suppository model; The experiments such as influence of the leucocyte consumption that Herba Houttuyniae gives thrombosis to be caused behind the rat suppository model have proved that Herba Houttuyniae has control thrombosis, anticoagulant new role.Therefore, the purpose of this invention is to provide Herba Houttuyniae and prevent and/or treat the application in the thrombosis medicine, application in the preparation anticoagulation medicine and the application in the pharmaceutical composition of preparation treatment cardiovascular disease in preparation.
Technical solution:
Content of the present invention is: provide Herba Houttuyniae to prevent and/or treat the new application in the thrombosis medicine in preparation, the new application in the preparation anticoagulation medicine.
Described Herba Houttuyniae is the extract of bright or dried Herba Houttuyniae herb, ground or under ground portion, and its preparation can be taked following method:
1. get aquatic foods or dried Herba Houttuyniae 1000g and carry out vapor distillation, collect distillate 1000ml, carry out redistillation again; Collect distillate 500ml; Add 3.5g sodium chloride and an amount of cosolvent (like polyoxyethylene sorbitan monoleate or solution HS15 or other acceptable cosolvents), mixing adds the injection water and makes into 1000ml; Filter sterilization.
2. get bright or dried Herba Houttuyniae 1000g, extract volatile oil with the Sha Shi extractor.Saturated aqueous solution with normal saline preparation volatile oil in order to improve the dissolubility of volatile oil, can add an amount of acceptable cosolvent (like polyoxyethylene sorbitan monoleate or solution HS15 or other acceptable cosolvents).
3. get bright or dried Herba Houttuyniae 100g, add the 800ml decocting and boil 20min to the boiling back, 2 times repeatedly, merge filtering liquid medicine, be concentrated into 200ml, making decocting liquid can use directly into preparation.In order to remove tannin, also can be with adding 95% ethanol in the decocting liquid again, after the stirring, hold over night.Take out supernatant, filter, behind the recovery ethanol, process 200ml liquid.
4. Herba Houttuyniae 200g is ground into segment, puts into the container of suitable volumes.Add ethanol or ether or petroleum ether 1200ml, the jam-pack bottleneck soaks 24~48h.Leach medicinal liquid, volatilize petroleum ether.
Product of the present invention comprises the medicine or the health product that relate to antithrombotic, anticoagulation related application that contain Herba Houttuyniae.
Product of the present invention comprises and relates to human that relates to antithrombotic, anticoagulation related application and the product for animals that contains Herba Houttuyniae.
It is active component that further aspect of the present invention also relates to the Herba Houttuyniae extract, is the pharmaceutical composition of indication with antithrombotic, anticoagulation.This pharmaceutical composition can be with the extract of the method described in the technical scheme of the present invention preparation, combines with one or more pharmaceutically acceptable solids or liquid excipient and/or adjuvant, processes any dosage form that is suitable for human or animal's use.Route of administration can be intestinal or parenteral route, as: oral, intravenous injection, intramuscular injection, subcutaneous injection, nasal cavity, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum etc.Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be solution (comprising true solution and colloid solution), Emulsion, microemulsion, suspensoid, injection (comprising aqueous injection, injectable powder and transfusion), eye drop, nasal drop, lotion, liniment etc.; Solid preparation can be tablet (comprising ordinary tablet, enteric coatel tablets, buccal tablet, dispersible tablet, chewable tablet, effervescent tablet, oral cavity disintegration tablet etc.), capsule (comprising hard capsule, soft capsule, enteric coated capsule), granule, powder, micropill, drop pill, suppository, membrane, paster, the agent of gas (powder) mist, spray etc.; Semi-solid preparation can be ointment, gel, paste etc.Preparation can be processed ordinary preparation, also can be slow releasing agent, controlled release agent, targeting preparation and various particulate delivery system.
Advantage that the present invention has and effect:
1. the Herba Houttuyniae resource is very extensive, and method for distilling is simple, can be made into pharmaceutical preparatioies such as injection, capsule, concentrated pill, granule, tablet, powder, oral liquid.
2. prove through animal experiment that Herba Houttuyniae can obviously suppress the thrombosis of thrombus model, significantly shortens thrombosis length, suppress because thrombosis descends with the platelet that blood coagulation causes the leukocyte count reduction in the inhibition thrombosis process.
Four, description of drawings
No accompanying drawing.
Five, the specific embodiment
Embodiment one: the boat thrombosis effect test of Herba Houttuyniae
1. Herba Houttuyniae method for preparing
Get aquatic foods or dried Herba Houttuyniae 1000g and carry out vapor distillation, collect distillate 1000ml, carry out redistillation again; Collect distillate 500ml; Add 3.5g sodium chloride and an amount of cosolvent (like polyoxyethylene sorbitan monoleate or solution HS15 or other acceptable cosolvents), mixing adds the injection water and makes into 1000ml; Filter sterilization.
2. animal experiment method:
Rat by random packet, 10 every group, is respectively: 1. normal group; 2. thrombus model group (carrageenin Ca/ endotoxin LPS modeling); 3. Herba Houttuyniae 24ml/kg; 4. Herba Houttuyniae 12ml/kg.Tested first day, and 3., 4. organized the rats by intraperitoneal injection Herba Houttuyniae, 1., 2. organize intraperitoneal injection of saline 5ml/kg, inject 1 time in the morning and afternoon respectively for every group; After afternoon, drug administration by injection finished (16:00pm), except normal group, other three groups equal lumbar injection carrageenin 25mg/kg.Subsequently, with animal fasting 16~18h.Next day, two dose groups of Herba Houttuyniae again intraperitoneal injection once, normal control group and model group be intraperitoneal injection of saline still.After the administration 30 minutes, the intravenous injection of normal control group gave normal saline 0.24ml/100g, and the animal of other three groups all gives endotoxin (LPS) 50 μ g/kg (every ml contains LPS 20 μ g) through intravenous injection.24h behind injection LPS is with the thrombosis length of kind of calliper rat tails.
3. antithrombotic result of the test
After adopting carrageenin/LPS modeling; Form thrombosis in the model group animal body, be in particular in the Animal Tails far-end, form the thrombosis length of about 5-9cm; Because thrombus obstruction arteria caudalis and vein blood vessel; And make corresponding tissue and skin be rendered as purple because of ischemia, therefore, thrombosis length is easy to measure.Visible from table 1 result, the thrombosis length of model group on average is about 7.7cm, and Herba Houttuyniae 24ml/kg and 12mg/kg all can suppress rat suppository and form, and wherein, 24ml/kg group and matched group relatively have the significant difference (P<0.05) of highly significant.The result shows that Herba Houttuyniae can obviously suppress thrombosis.
Annotate: compare with model group
*P<0.01
Embodiment two: the influence of the leucocyte consumption that Herba Houttuyniae causes thrombosis
1. Herba Houttuyniae method for preparing
Get aquatic foods or dried Herba Houttuyniae 1000g and carry out vapor distillation, collect distillate 1000ml, carry out redistillation again, collect distillate 500ml, add 3.5g sodium chloride and an amount of cosolvent, mixing adds the injection water and makes into 1000ml, filtration, sterilization.
2. animal experiment method
Rat by random packet, 10 every group, is respectively: 1. normal group; 2. thrombus model group (carrageenin Ca/ endotoxin LPS modeling); 3. Herba Houttuyniae 24ml/kg; 4. Herba Houttuyniae 12ml/kg.Tested first day, and 3., 4. organized the rats by intraperitoneal injection Herba Houttuyniae, 1., 2. organize intraperitoneal injection of saline 5ml/kg, inject 1 time in the morning and afternoon respectively for every group; After afternoon, drug administration by injection finished (16:00pm), except normal group, other three groups equal lumbar injection carrageenin 25mg/kg.Subsequently, with animal fasting 16~18h.Next day, two dose groups of Herba Houttuyniae again intraperitoneal injection once, normal control group and model group be intraperitoneal injection of saline still.After the administration 30 minutes, the intravenous injection of normal control group gave normal saline 0.24ml/100g, and the animal of other three groups all gives endotoxin (LPS) 50 μ g/kg (every ml contains LPS 20 μ g) through intravenous injection.4h (same day) behind injection LPS gets blood from the eye socket venous plexus, uses full-automatic blood counting instrument, measures the leucocyte consumption that thrombosis causes.
3. experimental result
According to thrombotic process, when thrombosis condenses, can assemble a large amount of leukocyte in the thrombosis, thereby cause the peripheral white blood cell amount to reduce, thrombosis is big more, and peripheral white blood cell is low more.Therefore the degree of peripheral white blood cell amount reduction can be reacted the thrombosis degree.This experimental result shows; Total white blood cells in the model group rat peripheral blood is decline 62% rapidly in 4 hours (comparing P<0.01 with the normal control group) after giving LPS; This is because thrombosis has been assembled a large amount of leukocyte, and causes the quantity of leucocyte in the peripheral circulation blood to descend rapidly.Herba Houttuyniae can suppress the leucocyte consumption that thrombosis causes, thereby makes the peripheral white blood cell amount obviously increase, and wherein the 24ml/kg dose groups increases approximately 40% than model group, and has statistical significant difference (P<0.05).Results suggest, Herba Houttuyniae can suppress thrombosis, thereby reduces the gathering of leukocyte at thrombosis, promotes circulation quantity of leucocyte in the peripheral blood.The result sees table 2.
Annotate: compare ##P<0.01 with matched group, compare with model group
*P<0.05,
*P<0.01
The influence of the platelet consumption that embodiment three, Herba Houttuyniae cause thrombosis
1. Herba Houttuyniae method for preparing
Get aquatic foods or dried Herba Houttuyniae 1000g and carry out vapor distillation, collect distillate 1000ml, carry out redistillation again, collect distillate 500ml, add 3.5g sodium chloride and an amount of cosolvent, mixing adds the injection water and makes into 1000ml, filtration, sterilization.
2. animal experiment method
Rat by random packet, 10 every group, is respectively: 1. normal group; 2. thrombus model group (carrageenin Ca/ endotoxin LPS modeling); 3. Herba Houttuyniae 24ml/kg; 4. Herba Houttuyniae 12ml/kg.Tested first day, and 3., 4. organized the rats by intraperitoneal injection Herba Houttuyniae, 1., 2. organize intraperitoneal injection of saline 5ml/kg, inject 1 time in the morning and afternoon respectively for every group; After afternoon, drug administration by injection finished (16:00pm), except normal group, other three groups equal lumbar injection carrageenin 25mg/kg.Subsequently, with animal fasting 16~18h.Next day, two dose groups of Herba Houttuyniae again intraperitoneal injection once, normal control group and model group be intraperitoneal injection of saline still.After the administration 30 minutes, the intravenous injection of normal control group gave normal saline 0.24ml/100g, and the animal of other three groups all gives endotoxin (LPS) 50 μ g/kg (every ml contains LPS 20 μ g) through intravenous injection.24h (next day) behind injection LPS gets blood from the eye socket venous plexus, uses full-automatic blood counting instrument, measures the platelet consumption that thrombosis causes.
3. experimental result
According to thrombotic process, when thrombosis condenses, can assemble a large amount of platelet in the thrombosis, thereby cause the peripheral blood platelet counts to reduce, thrombosis is big more, and the periphery platelet count is low more.This experimental result shows; Model group platelet count in the peripheral blood (PLT) after giving LPS 24h significantly descended for 62% (comparing P<0.01 with the normal control group); This is because thrombosis has been assembled a large amount of platelet, thereby causes the platelet counts in the peripheral circulation blood to descend rapidly.Herba Houttuyniae can significantly suppress platelet counts to be reduced, and wherein the 24ml/kg dose groups increases approximately 40% than model group, and has statistical significant difference (P<0.05).Results suggest, Herba Houttuyniae can suppress thrombosis, thereby reduces the gathering of platelet at thrombosis, promotes circulation platelet counts in the peripheral blood.The result sees table 3.
Annotate: compare ##P<0.01 with matched group, compare with model group
*P<0.05,
*P<0.01
Claims (3)
1. Herba Houttuyniae extract prevents and/or treats the application in the thrombosis medicine in preparation, it is characterized in that the method for preparing of described Herba Houttuyniae extract is carried out vapor distillation for getting aquatic foods or dried Herba Houttuyniae 1000g, collects distillate 1000ml; Carry out redistillation again, collect distillate 500ml, add 3.5g sodium chloride and an amount of cosolvent; Mixing; Add the injection water and make into 1000ml, filter sterilization.
2. application according to claim 1, Herba Houttuyniae extract is medicine or health product at the product that preparation prevents and/or treats the application in the thrombosis medicine.
3. application according to claim 1 is characterized in that, the described medicine that prevents and/or treats thrombosis is a human or for animals.
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