CN110507650A - Application of the Rhizoma Atractylodis Macrocephalae lactams in terms of preparing antithrombotic reagent - Google Patents
Application of the Rhizoma Atractylodis Macrocephalae lactams in terms of preparing antithrombotic reagent Download PDFInfo
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- CN110507650A CN110507650A CN201910970248.3A CN201910970248A CN110507650A CN 110507650 A CN110507650 A CN 110507650A CN 201910970248 A CN201910970248 A CN 201910970248A CN 110507650 A CN110507650 A CN 110507650A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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Abstract
The invention discloses application of the Rhizoma Atractylodis Macrocephalae lactams in terms of preparing antithrombotic reagent.In recent years, cardiovascular disease incidence rate persistently increases, and death toll caused by cardiovascular disease has occupied the first place of the various diseases death rate.The main reason for thrombotic diseases ratio in cardiovascular disease is very high, and wherein thrombosis caused by platelet function abnormality and embolic complications are cardiovascular disease incidences.Antithrombotic reagent is the important means for preventing and treating thrombotic diseases, and wherein Chinese medicine has antiplatelet and antithrombotic original curative effect, and Small side effects.The embodiment of the present invention shows that Rhizoma Atractylodis Macrocephalae lactams is low, high dose can be obviously prolonged mouse CT and BT, inhibits FeCl3Induced rat thrombosis, Rhizoma Atractylodis Macrocephalae lactams have apparent anticoagulation and antithrombotic effect, can be used for preparing antithrombotic reagent.
Description
Technical field
The invention belongs to field of medicaments, and in particular to application of the Rhizoma Atractylodis Macrocephalae lactams in terms of preparing antithrombotic reagent.
Background technique
In recent years, cardiovascular disease incidence rate persistently increases, and death toll caused by cardiovascular disease has occupied various diseases
The first place of the death rate.Thrombotic diseases ratio in cardiovascular disease is very high, wherein thrombus shape caused by platelet function abnormality
The main reason at being cardiovascular disease incidence with embolic complications.
Thrombotic diseases are one kind diseases as caused by two kinds of pathologic processes of thrombosis and thromboembolism, the former refers to blood
Visible component in liquid forms embolus in the blood vessel, causes vasculature part or completely plugged；The latter then refers to thrombus self-forming portion
Position falls off, and certain blood vessels are partly or entirely blocked with blood circulation.Thrombotic diseases have the characteristics of high mortality and high disability rate,
Wherein platelet activation is the important pathological basis of thrombosis extremely.
Antithrombotic reagent is the important means for preventing and treating thrombotic diseases, and wherein Chinese medicine and its preparation have solely antithrombotic
The curative effect arrived, and Small side effects, thus the native compound for being found to have from Chinese medicine and its preparation antithrombotic acitivity is always
The hot spot of antithrombotic reagent research field.The discovery such as Song Qiling, part veratrum alkaloid have apparent anti thrombotic action, specifically
Related with the chemical structure of veratrum alkaloid, there are apparent structure-activity relationship (veratrum alkaloid anti thrombotic action and structure effects for drug effect
Relationship research, Chinese medicine, the o. 11th of volume 37 in November, 2014).The discovery such as Wan Yanjun, onocerin sodium sulfonate height, middle dosage
Group can inhibit rat suppository formation, platelet aggregation, extend mouse bleeding time (BT) and Activated partial thromboplastin time
(APTT), has the function of inhibition thrombosis, mechanism of action may have with it inhibits ADP, thrombin induction blood platelet
Aggregation reduces the function of endogenous coagulation pathway in relation to (onocerin sodium sulfonate anti thrombotic action and Mechanism Study, Chinese new drug are miscellaneous
Will the 12nd phase of volume 25 in 2016).Wan Xiaochen etc. has found that the high, medium and low dosage group of diosmin can obviously inhibit in Galium verum
Rat inferior vena cava thrombosis is formed, and protects vascular endothelial cell, and middle dose group is suitable with aspirin group effect, shows spiceleaf
The wooden glycosides has the function of that (experiment of diosmin anti-thrombosis function is ground in Galium verum for anticoagulation and anti-venous thronbosis
Study carefully, traditional Chinese medicine information, the 6th phase of volume 31 in November, 2014).
Rhizoma Atractylodis Macrocephalae lactams (Atractylenolactam) is a kind of amides native compound, and chemical structure is as follows.
There is presently no be disclosed for the anti thrombotic action of Rhizoma Atractylodis Macrocephalae lactams.
Summary of the invention
The purpose of the present invention is to provide application of the Rhizoma Atractylodis Macrocephalae lactams in terms of preparing antithrombotic reagent.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
Application of the Rhizoma Atractylodis Macrocephalae lactams in terms of preparing antithrombotic reagent.
A kind of antithrombotic reagent, active constituent are Rhizoma Atractylodis Macrocephalae lactams.
Further, antithrombotic reagent also contains pharmaceutically acceptable auxiliary material, and pharmaceutically acceptable agent is made
Type.
Further, the auxiliary material includes liquid, solid or semisolid auxiliary material.
Further, the dosage form includes tablet, capsule, injection.
The utility model has the advantages that
In recent years, cardiovascular disease incidence rate persistently increases, and death toll caused by cardiovascular disease has occupied various diseases
The first place of the death rate.Thrombotic diseases ratio in cardiovascular disease is very high, wherein thrombus shape caused by platelet function abnormality
The main reason at being cardiovascular disease incidence with embolic complications.Antithrombotic reagent is the important hand for preventing and treating thrombotic diseases
Section, wherein Chinese medicine has antiplatelet and antithrombotic original curative effect, and Small side effects.The embodiment of the present invention shows white
Art lactams is low, high dose can be obviously prolonged mouse CT and BT, inhibits FeCl3Induced rat thrombosis, Rhizoma Atractylodis Macrocephalae lactams
With apparent anticoagulation and antithrombotic effect, can be used for preparing antithrombotic reagent.
Detailed description of the invention
Fig. 1 is each group mouse CT (unit: s)；
Fig. 2 is each group mouse BT (unit: s)；
Fig. 3 is each group rat suppository quality (unit: mg).
Specific embodiment
Essentiality content of the present invention is specifically introduced below with reference to embodiment, but does not limit protection model of the invention with this
It encloses.
Embodiment 1: influence of the Rhizoma Atractylodis Macrocephalae lactams to the clotting time
Kunming kind healthy mice is taken, 18~22g of weight, be randomly divided into 4 groups: control group, positive drug group, Rhizoma Atractylodis Macrocephalae lactams are low
Dosage administration group, Rhizoma Atractylodis Macrocephalae lactams high dose administration group, every group 6.50mg/kg/d aspirin is given in positive drug group stomach-filling,
Rhizoma Atractylodis Macrocephalae lactams is low, 20mg/kg/d, 50mg/kg/d Rhizoma Atractylodis Macrocephalae lactams, control group stomach-filling are given in stomach-filling to high dose administration group respectively
Isometric solvent 0.5%CMC-Na solution, successive administration 7d.After last time administration 1h, the clotting time is measured using slide method
(CT).Method particularly includes: eyeball of mouse blood sampling respectively drips 1 in glass slide both ends and bleeds, drop of blood diameter about 5mm, immediately with stopwatch meter
When, it is gently provoked inwards 1 time every 10s with cleaning pin autoblood edge, and whether there is or not the traces of blood to provoke for observation.Since blood sampling
It is CT to the trace of blood time is provoked, CT longest observes 15min, and it is noncondensing more than 15min to be calculated by 30min, it is another to bleed again
Examination.Each group CT is calculated, is analyzed using SPSS17.0 software, data are indicated with mean ± standard deviation, and comparison among groups use One-
WayANOVA is examined, and it is statistically significant that P < 0.05 represents difference.
As a result as shown in table 1 and Fig. 1, compared with the control group, positive drug group, Rhizoma Atractylodis Macrocephalae lactams low dosage administration group, Rhizoma Atractylodis Macrocephalae
The CT of lactams high dose administration group mouse is obviously prolonged, and difference has statistical significance, and Rhizoma Atractylodis Macrocephalae lactams is low, high agent
It measures administration group and dose dependent is presented to the extension effect of CT.
1 each group mouse CT of table
| Group | CT (unit: s) |
| Control group | 56.7±8.2 |
| Positive drug group | 88.3±7.5 |
| Rhizoma Atractylodis Macrocephalae lactams low dosage administration group | 76.7±8.2 |
| Rhizoma Atractylodis Macrocephalae lactams high dose administration group | 98.3±7.5 |
Embodiment 2: influence of the Rhizoma Atractylodis Macrocephalae lactams to the bleeding time
Kunming kind healthy mice is taken, 18~22g of weight, be randomly divided into 4 groups: control group, positive drug group, Rhizoma Atractylodis Macrocephalae lactams are low
Dosage administration group, Rhizoma Atractylodis Macrocephalae lactams high dose administration group, every group 6.50mg/kg/d aspirin is given in positive drug group stomach-filling,
Rhizoma Atractylodis Macrocephalae lactams is low, 20mg/kg/d, 50mg/kg/d Rhizoma Atractylodis Macrocephalae lactams, control group stomach-filling are given in stomach-filling to high dose administration group respectively
Isometric solvent 0.5%CMC-Na solution, successive administration 7d.After last time administration 1h, mouse bleeding is measured using docking method
Time (BT).Method particularly includes: mouse is fixed, is measured and rat-tail length and is marked with milimeter scale, then with operating scissors by mouse
It is cross-section at tail point 4mm, it is voluntarily overflowed to blood and starts timing, it is primary with filter paper to suck drop of blood every 10s, until blood flow stops naturally
Only until while inhaling (filter paper without blood), as BT.BT longest observes 30min, more than calculating by 30min for 30min still bleeding.It calculates
Each group BT is analyzed using SPSS17.0 software, and data are indicated with mean ± standard deviation, and comparison among groups are examined using One-wayANOVA
It tests, it is statistically significant that P < 0.05 represents difference.
As a result as shown in table 2 and figure 2, compared with the control group, positive drug group, Rhizoma Atractylodis Macrocephalae lactams low dosage administration group, Rhizoma Atractylodis Macrocephalae
The BT of lactams high dose administration group mouse is obviously prolonged, and difference has statistical significance, and Rhizoma Atractylodis Macrocephalae lactams is low, high agent
It measures administration group and dose dependent is presented to the extension effect of BT.
2 each group mouse BT of table
Embodiment 3: influence of the Rhizoma Atractylodis Macrocephalae lactams to thrombus production quantity
Take cleaning grade male SD rat, weight 260-280g is randomly divided into 4 groups: control group, positive drug group, acyl in Rhizoma Atractylodis Macrocephalae
Amine low dosage administration group, Rhizoma Atractylodis Macrocephalae lactams high dose administration group, every group 6.Rhizoma Atractylodis Macrocephalae lactams is low, high dose administration group fills respectively
Stomach gives 20mg/kg/d, 50mg/kg/d Rhizoma Atractylodis Macrocephalae lactams, the isometric solvent 0.5%CMC-Na solution of control group stomach-filling, continuously
7d is administered, positive drug group is in the 6th, 7d respectively at dorsal sc injection 2000U/kg/d heparin sodium.After last time administration 2h, use
3% yellow Jackets anesthetized rat, abdomen median incision open abdominal cavity, separate aortic segment.Then with being impregnated with 50% completely
FeCl3The filter paper item (1.0cm × 2.0cm) of solution is encircled in the aortic segment isolated, along filter paper ring edge after 50min
Accurate interception 1.0cm long vessel segment, blots the remained blood in blood vessel, accurately weighed quality, will remove the blood vessel after thrombus again
The quality as thrombus in the 1.0cm long vessel segment is subtracted each other in secondary accurately weighed quality, both front and backs.Each group thrombus quality is calculated,
It is analyzed using SPSS17.0 software, data are indicated with mean ± standard deviation, and comparison among groups are examined using One-wayANOVA, P <
0.05 to represent difference statistically significant.
As a result as shown in table 3 and figure 3, compared with the control group, positive drug group, Rhizoma Atractylodis Macrocephalae lactams low dosage administration group, Rhizoma Atractylodis Macrocephalae
The thrombus quality of lactams high dose administration group rat is substantially reduced, and difference has statistical significance, and Rhizoma Atractylodis Macrocephalae lactams is low, high
Dose dependent is presented to the reduction effect of thrombus in dosage administration group.
3 each group rat suppository quality of table
| Group | Thrombus quality (unit: mg) |
| Control group | 9.5±1.2 |
| Positive drug group | 2.3±0.5 |
| Rhizoma Atractylodis Macrocephalae lactams low dosage administration group | 5.6±0.7 |
| Rhizoma Atractylodis Macrocephalae lactams high dose administration group | 3.1±0.8 |
In recent years, cardiovascular disease incidence rate persistently increases, and death toll caused by cardiovascular disease has occupied various diseases
The first place of the death rate.Thrombotic diseases ratio in cardiovascular disease is very high, wherein thrombus shape caused by platelet function abnormality
The main reason at being cardiovascular disease incidence with embolic complications.Antithrombotic reagent is the important hand for preventing and treating thrombotic diseases
Section, wherein Chinese medicine has antiplatelet and antithrombotic original curative effect, and Small side effects.The embodiment of the present invention shows white
Art lactams is low, high dose can be obviously prolonged mouse CT and BT, inhibits FeCl3Induced rat thrombosis, Rhizoma Atractylodis Macrocephalae lactams
With apparent anticoagulation and antithrombotic effect, can be used for preparing antithrombotic reagent.
The effect of above-described embodiment is specifically to introduce essentiality content of the invention, but those skilled in the art should know
Protection scope of the present invention should not be confined to the specific embodiment by road.
Claims (5)
1. application of the Rhizoma Atractylodis Macrocephalae lactams in terms of preparing antithrombotic reagent.
2. a kind of antithrombotic reagent, which is characterized in that active constituent is Rhizoma Atractylodis Macrocephalae lactams.
3. drug according to claim 2, which is characterized in that also containing pharmaceutically acceptable auxiliary material, pharmacy is made
Upper acceptable dosage form.
4. drug according to claim 3, which is characterized in that the auxiliary material includes liquid, solid or semisolid auxiliary material.
5. drug according to claim 3, which is characterized in that the dosage form includes tablet, capsule, injection.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114409588A (en) * | 2022-03-19 | 2022-04-29 | 河南中医药大学 | Novel compound of atractylenolide, preparation method and medical application |
| CN114436939A (en) * | 2022-03-19 | 2022-05-06 | 河南中医药大学 | Method for separating and preparing Taenialactam A and B of largehead atractylodes rhizome lactam |
| CN114558005A (en) * | 2022-03-19 | 2022-05-31 | 河南中医药大学 | Medical application of Largehead Atractylodes rhizome lactam Taenialactam A and B |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114409588A (en) * | 2022-03-19 | 2022-04-29 | 河南中医药大学 | Novel compound of atractylenolide, preparation method and medical application |
| CN114436939A (en) * | 2022-03-19 | 2022-05-06 | 河南中医药大学 | Method for separating and preparing Taenialactam A and B of largehead atractylodes rhizome lactam |
| CN114558005A (en) * | 2022-03-19 | 2022-05-31 | 河南中医药大学 | Medical application of Largehead Atractylodes rhizome lactam Taenialactam A and B |
| CN114436939B (en) * | 2022-03-19 | 2023-11-17 | 河南中医药大学 | Method for separating and preparing largehead atractylodes rhizome lactam Taenialactam A and B |
| CN114409588B (en) * | 2022-03-19 | 2023-11-17 | 河南中医药大学 | Atractylodes macrocephala lactam new compound, preparation method and medical application |
| CN114558005B (en) * | 2022-03-19 | 2024-03-08 | 河南中医药大学 | Medical application of largehead atractylodes rhizome lactam Taenialactam A and B |
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