CN104546953A - Application of moellendorf's spikemoss herb extract in preparation of medicines for treating thrombotic diseases - Google Patents

Application of moellendorf's spikemoss herb extract in preparation of medicines for treating thrombotic diseases Download PDF

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Publication number
CN104546953A
CN104546953A CN201510016292.2A CN201510016292A CN104546953A CN 104546953 A CN104546953 A CN 104546953A CN 201510016292 A CN201510016292 A CN 201510016292A CN 104546953 A CN104546953 A CN 104546953A
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China
Prior art keywords
extract
herba selaginellae
selaginellae involventis
preparation
moellendorf
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孔毅
苏杏丽
苏雯
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China Pharmaceutical University
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China Pharmaceutical University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/11Pteridophyta or Filicophyta (ferns)
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention relates to biological medicines and in particular relates to a moellendorf's spikemoss herb extract and an application of the moellendorf's spikemoss herb extract in preparation of medicines for treating thrombotic diseases. The moellendorf's spikemoss herb extract refers to an ethanol extract of a whole moellendorf's spikemoss herb. The preparation method comprises the following steps: cutting the whole moellendorf's spikemoss herb into pieces with the length of about 3mm, adding 70 percent ethanol solution, and soaking for 9 hours; performing reflux extraction for 3 hours at the extraction temperature of 40-45 DEG C, slightly cooling, filtering by using a gauze to obtain the filtrate, and remaining the moellendorf's spikemoss herb residues; adding 70 percent ethanol solution into the moellendorf's spikemoss herb residues again, performing secondary heating and reflux extraction; and mixing the filtrates obtained by the extraction twice, performing vacuum concentration at the temperature of 50 DEG C or below, recovering the ethanol until the alcohol flavor is avoided, performing freeze drying, thereby obtaining the moellendorf's spikemoss herb extract. The extract has anti-thrombus and anti-platelet aggregation activities and can serve as a drug candidate for treating the thrombotic diseases to be developed.

Description

The application of a kind of Herba Selaginellae Involventis extract in preparation treatment thrombotic disease medicine
Technical field
The present invention relates to biomedicine field, be specifically related to the novel medical use that a kind of Herba Selaginellae Involventis water or alcohol water extract and this extract are used for the treatment of thrombotic disease.
Background technology
Thrombotic disease is that the lumen of vessels that caused by thrombosis is narrow in obturation, makes main organs generation ischemia and infraction and causes the various diseases of malfunction, belonging to cardiovascular and cerebrovascular disease.The normal hemostasis-coagulation of body, depends on complete wall structures and function, effective platelet quality and quantity, normally plasma coagulation factors are active.Thrombotic reason, be briefly the growth along with people's age, in body, Fibrinolytic System reduces gradually, blood coagulation and anticoagulant functions disequilibrium in blood and occur blood coagulation, i.e. thrombosis.
The sickness rate of thrombotic disease, fatality rate and disability rate are very high.It is one of disease of serious harm human health, is also the focus of countries in the world medicine scholar research.3 classes to be divided into clinically, antiplatelet medicine, anticoagulant medicine and thrombolytic medicine at present for the drug main of thrombus prevention and treatment.New active component is found from natural product, and and then to develop new medicine be also the important channel capturing clinical persistent ailment now, the present invention provides scientific basis by carrying out activity research to Herba Selaginellae Involventis ethanol extraction to the medicine for finding new antithrombotic disease.
Herba Selaginellae Involventis (Selaginella moellendorfii Hieron.) is a kind of perennial evergreen herbaceous plant, is the Chinese herbal medicine that China is conventional.Its property is put down, and taste is micro-sweet, energy clearing away heat and promoting diuresis, promoting blood circulation and detumescence.Modern pharmacological research shows that it has pharmacologically active widely, such as anti-tumor activity, antibacterial activity, antiviral and immunoregulatory activity, is used to the diseases such as treatment acute infectious hepatitis, the contusion of breast side of body waist, anasarca.
Herba Selaginellae Involventis extract be a kind of from the overall plant of Herba Selaginellae Involventis through mixture that water or alcohol water extraction obtain.Current home and abroad is more to Herba Selaginellae Involventis research, but does not have Herba Selaginellae Involventis extract preparing the report of the research in resisting thrombotic diseases medicine.
Summary of the invention
In order to meet clinical needs, solve the problem, the object of this invention is to provide a kind of Herba Selaginellae Involventis extract and the application in treatment thrombotic disease medicine thereof; Herba Selaginellae Involventis extract can be used as in the medicine of active ingredient for the preparation for the treatment of thrombotic disease, namely can be used for preventing and/or treating in the medicine of the diseases such as coronary heart diseases and angina pectoris, cerebral thrombosis or pulmonary infarction.
For achieving the above object, the technical solution used in the present invention is:
Herba Selaginellae Involventis extract, it is water or the alcohol water extract of whole strain Herba Selaginellae Involventis.
Water or the concrete preparation process of alcohol water extract of described Herba Selaginellae Involventis are:
1) whole strain Herba Selaginellae Involventis is shredded into the fragment being about 3mm, add 70% alcohol solution dipping 9h, then reflux, extract, 3h, Extracting temperature 40-45 DEG C, slightly cold, by filtered through gauze, obtain filtrate, retain filtering residue.In filtering residue, add 70% alcoholic solution again carry out post bake reflux, extract.
During described each reflux, extract, the consumption of 70% ethanol is 4 times (V/W) of Herba Selaginellae Involventis quality.
2) merge above-mentioned extracted twice gained filtrate, concentrating under reduced pressure below 50 DEG C, obtain the Herba Selaginellae Involventis extract with antiplatelet aggregation and antithrombotic acitivity.
3) described filtrate can adopt concentrate drying, lyophilization or spray drying process drying to be solid after concentrating under reduced pressure, obtains the extract with treatment thrombotic disease.
Described extract is for the preparation of preventing and/or treating thrombotic disease medicine, preventive health care's food of thrombotic disease or food additive.
The medicine that described preparation prevents and/or treats thrombotic disease refers to that the pharmaceutical dosage form of claim 1 made by it can be pill, powder, tablet, unguentum, powder, injection, water preparation, granule or injection.
The described medicine preventing and/or treating thrombotic disease is combined as excipient as active component with acceptable carrier on materia medica by described plant extract, conventionally makes the dosage form for oral administration of oral administration or the injection of non-oral administration; Namely can be prepared as the medicine of the various dosage form such as pill, powder, tablet, unguentum, powder, injection, water preparation, granule, injection of the diseases such as treatment coronary heart diseases and angina pectoris, cerebral thrombosis or pulmonary infarction; Health food form can be liquid such as refreshment drink etc.
In application of the present invention, described thrombotic disease is the arterial thrombotic disease caused by platelet aggregation.
Pharmacological effect experiment confirms, Herba Selaginellae Involventis extract energy of the present invention is effective, the suppression extracorporeal platelet aggregation of dose dependent, reduce chmice acute lung thrombosis mortality rate, can antithrombotic reagent be prepared as, particularly the arterial thrombus medicine that causes of antiplatelet aggregation.
Tool of the present invention has the following advantages:
Herba Selaginellae Involventis extract is as the main component of natural Chinese medicine extract, its abundance, cheap, has the advantages such as high antithrombotic acitivity, can be widely used in the arterial cardiovascular such as atherosclerosis, myocardial infarction disease.
Accompanying drawing explanation
Fig. 1 is the analysis chart of Herba Selaginellae Involventis extract In Vitro Anti platelet aggregation test result of the present invention.
Detailed description of the invention
Concrete steps of the present invention are described by the following examples, but do not limit by embodiment.
Term used in the present invention, except as otherwise noted, generally has the implication that those of ordinary skill in the art understand usually.
Below in conjunction with specific embodiment and comparable data describes in further detail the present invention.Should be understood that these embodiments just in order to demonstrate the invention, but not limit the scope of the invention by any way.
In the examples below, the various process do not described in detail and method are conventional methods as known in the art.
The preparation of embodiment 1 Herba Selaginellae Involventis extract
Whole strain Herba Selaginellae Involventis (500g) is shredded into the fragment being about 3mm, adds 70% alcohol solution dipping 9h, then the reflux, extract, 3h of 8L, Extracting temperature 40-45 DEG C, slightly cold, by filtered through gauze, obtain filtrate, retain filtering residue.70% alcoholic solution adding 8L again in filtering residue carries out post bake reflux, extract.Merge above-mentioned extracted twice gained filtrate, concentrating under reduced pressure below 50 DEG C, lyophilization, obtains Herba Selaginellae Involventis extract.
Embodiment 2 external activity is tested: Herba Selaginellae Involventis extract (the being called for short Ps1) impact on platelet aggregation
Rabbit carotid artery gets blood, is placed in the 15ml centrifuge tube (often manage final volume and be about 10ml, ensure that Sanguis Leporis seu oryctolagi and anticoagulant volume ratio are 9: 1) of 3.8% sodium citrate containing 1ml; The centrifugal 5min of 1000r/min, get upper liquid and platelet rich plasma (platelet rich plasma, PRP), remaining blood sample is with the centrifugal 10-15min of 3000r/min, obtain platelet poor plasma (platelet poor plasma, PPP).PC is adjusted to (250 ~ 300) × 10 with PPP 9individual/L; Each test absorption 300 μ l PPP is placed in the zeroing of platelet aggregation instrument test section, then draws 270 μ l PRP and be placed in fore-warmer tank, adds given the test agent and the test pearl of variable concentrations gradient respectively; Under 37 DEG C of conditions, preheating 5min is placed on test section; Finally add 10 μ l and be correlated with derivant as ADP (French Hyphen Biomed company, final concentration 10 μMs), thrombin (French Hyphen Biomed company, final concentration 2U/ml) or U46619 (Sigma-Aldrich, final concentration 6 μMs); Hematoblastic maximum agglutination rate (RPA) in the upper mensuration 5min of LBY-NJ4 platelet aggregation instrument (Beijing Puli is raw); Wherein, blank is normal saline; Experiment in triplicate, passes through following formulae discovery platelet aggregation inhibition rate simultaneously:
Platelet aggregation inhibition rate=[(X-Y)/X] × 100%.X represents normal saline group maximum platelet aggregation rate; Y represents given the test agent maximum platelet aggregation rate.
Result shows, and increase with concentration, max platelet rate reduces gradually, and its inhibitory action presents the rising (as shown in Figure 1) of concentration dependent.
Embodiment 3 animal intracorporeal active experiment: Herba Selaginellae Involventis extract is on the impact of chmice acute lung thrombosis
1) laboratory animal: ICR mice (18-22g) 60, male and female half and half, purchased from Nanjing Qinglongshan animal center.
2) experimentation: mice is divided into 5 groups, often organizes 10, is respectively negative control group (normal saline replaces sample and derivant); Model control group (normal saline replacement sample); Positive controls (giving isopyknic aspirin); Basic, normal, high dose sample group (18,55,165mg/kg).Administration volume is 5ml/kg.After administration 30min, tail vein injection ADP (450mg/kg), makes mice form acute pulmonary thromboembolism, the quantity of the dead mice of the interior each group of 15min after record injection mixing derivant.Calculate the mortality rate often organized and by the protective rate of following formulae discovery anti-thrombus activity thing acute pulmonary thromboembolism.
Protective rate=[1-(X/Y)] × 100% of anti-thrombus activity material acute pulmonary thromboembolism.X represents the quantity of each group of dead mice; Y represents the total mice amount of each group.
Herba Selaginellae Involventis extract shown in table 1 is on the impact of chmice acute lung thrombosis
Compared with model control group, Herba Selaginellae Involventis extract brings out to ADP the protective effect that the death of mouse lung thrombosis has concentration dependent, illustrates that it has certain therapeutical effect to acute pulmonary embolism.
In sum, Herba Selaginellae Involventis extract of the present invention has significant inhibitory action to extracorporeal platelet aggregation, significantly can lower the mortality rate of acute lung thrombosis mice, can be used for preparing antithrombotic, particularly the medicine of arterial thrombus that causes of platelet aggregation.

Claims (6)

1. Herba Selaginellae Involventis extract, is characterized in that: it is water or the alcohol water extract of whole strain Herba Selaginellae Involventis.
2. Herba Selaginellae Involventis extract according to claim 1, is characterized in that: whole strain Herba Selaginellae Involventis is shredded into the fragment being about 3mm, adds 70% alcohol solution dipping 9h, then reflux, extract, 3h, reflux temperature 40-45 DEG C are slightly cold, by filtered through gauze, obtain filtrate, retain Herba Selaginellae Involventis slag.In Herba Selaginellae Involventis slag, add 70% alcoholic solution again and carry out post bake reflux, extract.Merge above-mentioned extracted twice gained filtrate, concentrating under reduced pressure below 50 DEG C, lyophilization, obtain the Herba Selaginellae Involventis extract with treatment thrombotic disease.
3. the preparation method of Herba Selaginellae Involventis extract according to claim 2, is characterized in that: during each reflux, extract, the consumption of 70% ethanol is 4 times (V/W) of Herba Selaginellae Involventis quality.
4. the preparation method of Herba Selaginellae Involventis extract according to claim 2, it is characterized in that: described filtrate can adopt concentrate drying, lyophilization or spray drying process drying to be solid after concentrating under reduced pressure recycling design, obtains the plant extract with treatment thrombotic disease.
5. the application of Herba Selaginellae Involventis extract in preparation treatment thrombotic disease medicine, is characterized in that: described Herba Selaginellae Involventis extract is for the preparation of the medicine for the treatment of thrombotic disease, preventive health care's food for the treatment of thrombotic disease or the food additive for the purpose of preventing and/or treating; The water that described Herba Selaginellae Involventis extract is Herba Selaginellae Involventis described in claim 1 or alcohol water extract.
6. the application of Herba Selaginellae Involventis extract in preparation treatment thrombotic disease medicine according to claim 5, it is characterized in that: the medicine of the treatment thrombotic disease for the purpose of described preparation prevents and/or treats refers to that Herba Selaginellae Involventis extract described in claim 1 combines as excipient with acceptable carrier on materia medica as active component, and the pharmaceutical dosage form made by it can be pill, powder, tablet, unguentum, powder, injection, water preparation, granule or injection.
CN201510016292.2A 2015-01-08 2015-01-08 Application of moellendorf's spikemoss herb extract in preparation of medicines for treating thrombotic diseases Pending CN104546953A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110558446A (en) * 2019-09-09 2019-12-13 青岛科技大学 Natural plant extract composition for poultry feed additive, preparation method and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09263541A (en) * 1996-03-29 1997-10-07 Sunstar Inc Cosmetic composition and medicinal composition containing aqueous extract of selaginella moellendorfii hieron
JPH09263526A (en) * 1996-03-29 1997-10-07 Sunstar Inc Cosmetic composition and medicinal composition containing extract of a plant in selaginella
CN101530438A (en) * 2009-04-17 2009-09-16 广州白云山制药股份有限公司广州白云山制药总厂 Medicine for treating thrombocytopenic purpura and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09263541A (en) * 1996-03-29 1997-10-07 Sunstar Inc Cosmetic composition and medicinal composition containing aqueous extract of selaginella moellendorfii hieron
JPH09263526A (en) * 1996-03-29 1997-10-07 Sunstar Inc Cosmetic composition and medicinal composition containing extract of a plant in selaginella
CN101530438A (en) * 2009-04-17 2009-09-16 广州白云山制药股份有限公司广州白云山制药总厂 Medicine for treating thrombocytopenic purpura and preparation method thereof

Non-Patent Citations (3)

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Title
ZHEN-XING ZOU等: ""A new pyrrole alkaloid from Selaginella moellendorfii Hieron"", 《CHINESE CHEMICAL LETTERS》 *
殷丹等: ""正交试验优选江南卷柏总黄酮提取工艺"", 《中国药房》 *
邓祥坚等: ""江南卷柏对家兔血小板聚集的影响"", 《广州医药》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110558446A (en) * 2019-09-09 2019-12-13 青岛科技大学 Natural plant extract composition for poultry feed additive, preparation method and application thereof

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Application publication date: 20150429