CN109432090A - A kind of application of cucurbit(7)uril - Google Patents
A kind of application of cucurbit(7)uril Download PDFInfo
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- CN109432090A CN109432090A CN201811571407.4A CN201811571407A CN109432090A CN 109432090 A CN109432090 A CN 109432090A CN 201811571407 A CN201811571407 A CN 201811571407A CN 109432090 A CN109432090 A CN 109432090A
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
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- A—HUMAN NECESSITIES
- 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 a kind of application of cucurbit(7)uril in blood anticoagulant drug.
Description
Technical field
The present invention relates to a kind of application of cucurbit(7)uril, application of especially a kind of cucurbit(7)uril in terms of anticoagulation.
Background technique
Cucurbit(7)uril (Cucurbit [7] urils) also known as cucurbit [7] urea, be by glycosides urea unit by methylene-bridged
The big ring cage compound with special hydrophobicity cage body and hydrophily port come.Melon ring can be with a variety of inorganic or organic point
Son forms stable host-guest packet by non-covalent bonds weak interactions such as cage body effect, hydrogen bond, Van der Waals force and ion dipoles
Tie complex, studies at home and abroad show that melon ring be it is nontoxic, can be used as a kind of safe drug carrier.But itself pharmacology of melon ring is made
With there is not been reported.
Cardiovascular and cerebrovascular disease is the general designation of cardiovascular disease and cranial vascular disease, refer to due to hyperlipidemia, blood is sticky,
The common name of ischemic or hemorrhagic disease occurs for heart caused by atherosclerosis, hypertension, brain and body tissue, is
One kind seriously threatening the mankind, and the common disease of especially 50 years old or more middle-aged and the old's health, cardiovascular and cerebrovascular disease is died of in the whole world every year
The number of disease is up to 15,000,000 people, and it is the first to occupy the various causes of the death.Thromboembolism is the most crucial pathologic process of cardiovascular disease.At present
The drug for treating cardiovascular and cerebrovascular mainly has two major classes: one kind is simple expansion blood vessel, and another kind of is thrombolysis fat melting class.It is molten in thrombolysis
In lipid drug, common anticoagulation medicine has heparin class, Coumarins, antiplatelet drug and thrombolysis enzyme.Clinically use
Antithrombotic reagent heparin, discovered in recent years cannot inhibit the fibrin ferment in conjunction with fibrin, this has become recurrence of thrombus
Key factor.With people to its study of incident mechanism and understanding deepen continuously and drug design and screening technique day by day
Maturation, research safety is effective, the anticoagulation suitable for long-term use, antithrombotic reagent are of great significance.
Summary of the invention
The object of the present invention is to provide a kind of applications of cucurbit(7)uril.The present invention is a kind of new opplication of cucurbit(7)uril,
The purposes of cucurbit(7)uril has been expanded, meanwhile, it is of great significance for the research and development of anticoagulation, antithrombotic reagent.
A kind of technical solution of the present invention: the application of cucurbit(7)uril in blood anticoagulant drug.
A kind of blood anticoagulant contains cucurbit(7)uril in the blood anticoagulant.
Coagulation process is a series of enzymatic catalysis as a result, the process can be divided into exogenous cruor pathway
(extrinsicpathway, EP), intrinsic coagulation pathway (intrinsic pathway, IP) and common coagulation pathway
(commonpathway,CP).Different closely related, the activation of blood clotting and the activated pathway of Stuart factor and coagulation factor
The measurement of partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB)
It is the important indicator that people judge the hemostasis of body and whether blood coagulation system occurs pathological change.What APTT mainly reflected be
Under the participation of Ca2+, fibrinogen is changed into the time required for insoluble fibrin；What PT mainly reflected is in blood plasma
The general activity of prothrombin, V, VIII, X and I；TT mainly reflects that fibrinogen is changed into needed for insoluble fibrin
The time wanted；FIB mainly reflects the content of fibrinogen.Wherein, PT is the index for reflecting exogenous cruor pathway, endogenous system
The inhibition of system fibrin ferment is related with the extension of TT and APTT.According to important Testing index PT, TT and APTT of blood plasma coherent condition,
Concrete analysis coagulation process is the result of the enzymatic catalysis of which coagulation pathway；This three is basic blood coagulation way independent
Diameter screening index has reacted the coagulation of intrinsic coagulation pathway, exogenous cruor pathway and common coagulation pathway respectively.
This patent is tested using blood coagulation resisting function, influence of the cucurbit(7)uril to the external clotting time (CT) of rabbit and
Influence to indexs such as thrombin time (TT), prothrombin time (PT) and Activated partial thromboplastin times (APTT), evaluation
Cucurbit(7)uril blood coagulation resisting function, the novel anticoagulants to develop safe and non-toxic provide new resource and approach.
Cucurbit(7)uril is obtained with significant anticoagulant active by using blood coagulation four detections, be can be used as and is used to prepare
Anticoagulation medicine uses.
Specific embodiment
Below with reference to embodiment, the present invention is further illustrated, but is not intended as the foundation limited the present invention.
The embodiment of the present invention
Embodiment: cucurbit(7)uril anticoagulant active experiment
(1) preparation of sample
It weighs cucurbit(7)uril 1mg and is dissolved in the solution for being made that concentration is 5mg/mL in 200 μ L physiological saline, precision weighs lamp
Small cup florigen 8mg is dissolved in the solution for being made that concentration is 13.33mg/mL in 600 μ L physiological saline.Precision weighs Yunnan Baiyao 1mg
It is dissolved in 200 μ L physiological saline and concentration is made as the solution of 5mg/mL, while configuring blank solvent control group.It is real with rabbit
Animal is tested, PT detection kit, APPT detection kit, TT detection kit, FIB reagent box for detecting content are then utilized respectively
It is measured.
Blood 3.6mL is taken from male beaver rabbit auricular vein, is placed on the centrifugation containing 400 μ L (0.109mol/L) of sodium citrate
Guan Zhong is mixed gently, and is centrifuged 15min under 3000rpm, is taken supernatant.
(2) measurement of APTT
25 μ L of sample solution is added with (1) in the preparation method of sample first in test cup, add 100 μ L of blood plasma with
And 100 μ L APTT reagents of 37 DEG C of pre-temperatures, 37 DEG C of incubation 5min finally add 100 μ L CaCl under 37 DEG C of pre-temperatures2It is molten
Liquid (0.025mol/L) records time, as APTT value.
(3) measurement of PT
The preparation method of sample is the same as (1).25 μ L of sample solution is added first in test cup, 100 μ L of blood plasma is then added,
It is put into insulating box and is incubated for 3min at 37 DEG C, be eventually adding the 200 μ L PT reagents of 37 DEG C of pre-temperatures, record time, as PT value.
(4) measurement of TT
The preparation method of sample is the same as (1).200 μ L of 50 μ L of sample solution and blood plasma, constant temperature are separately added into test cup
It is incubated for 3min in case, 200 μ L TT reagents 200 are then added, records time, as TT value.
(5) measurement of FIB
The preparation method of sample is the same as (1).Standard curve is established according to reagent specification method.Take respectively blood plasma, sample and
200 μ L of buffer, 100 μ L and 700 μ L are mixed, and 200 μ L blood plasma are taken out after dilution, are put into 37 DEG C of pre-temperatures in insulating box
Then 100 μ L thrombin solutions are added in 3min, record numerical value, are FIB value.
As a result it is indicated using arithmetic mean of instantaneous value and standard deviation, numerical statistic uses SPSS13.0 software one-way analysis of variance
Method compares its significant difference.
As a result it is as shown in the table:
Influence of 1 cucurbit(7)uril of table to blood plasma recalcification time
| APTT(S) | PT(S) | TT(S) | FIB(g/L) | |
| Blank | 19.50±0.10 | 14.70±0.27 | 14.8±0.10 | 7.98±0.05 |
| Yunnan Baiyao | 15.1±0.30### | 10.03±0.06### | 13.77±0.06## | 7.48±0.19## |
| Breviscapinun | 21.7±0.44### | 17.93±0.29### | 17.53±0.16### | 8.87±0.14### |
| Cucurbit(7)uril | 20.5±0.10##** | 14.80±0.56 | 13.93±0.16# | 8.35±0.18# |
Note: p < 0.01 #p < 0.05, ###p < 0.001,0.001 < ##p < 0.01,0.001 < * *
Four experiment displays of external blood coagulation, compared with blank group, cucurbit(7)uril extends APTT (p < 0.01) significantly, increases
FIB (p < 0.05) inhibits blood clotting by intrinsic coagulation pathway, but effect is weaker than positive control Breviscapinun.To sum up
Described, cucurbit(7)uril has certain Anticoagulant Activities in vitro, can be used as a kind of potential anticoagulant.
Claims (2)
1. a kind of application of cucurbit(7)uril in blood anticoagulant drug.
2. a kind of blood anticoagulant, it is characterised in that: contain cucurbit(7)uril in the blood anticoagulant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811571407.4A CN109432090B (en) | 2018-12-21 | 2018-12-21 | Application of seven-element cucurbituril |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201811571407.4A CN109432090B (en) | 2018-12-21 | 2018-12-21 | Application of seven-element cucurbituril |
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| Publication Number | Publication Date |
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| CN109432090A true CN109432090A (en) | 2019-03-08 |
| CN109432090B CN109432090B (en) | 2020-10-23 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111068102A (en) * | 2019-12-18 | 2020-04-28 | 陕西科技大学 | Enzyme-catalyzed blood-coagulation antibacterial controllable gelatin-based hydrogel and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104860952A (en) * | 2015-04-17 | 2015-08-26 | 贵州大学 | Extraction separation method of high-purity cucurbituril Q[7] |
| WO2018197705A1 (en) * | 2017-04-28 | 2018-11-01 | Benoit Prieur | Cucurbituril derivatives as oxygen carriers |
| CN109528715A (en) * | 2018-12-21 | 2019-03-29 | 贵州大学 | A kind of application of eight yuan of melon rings |
-
2018
- 2018-12-21 CN CN201811571407.4A patent/CN109432090B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104860952A (en) * | 2015-04-17 | 2015-08-26 | 贵州大学 | Extraction separation method of high-purity cucurbituril Q[7] |
| WO2018197705A1 (en) * | 2017-04-28 | 2018-11-01 | Benoit Prieur | Cucurbituril derivatives as oxygen carriers |
| CN109528715A (en) * | 2018-12-21 | 2019-03-29 | 贵州大学 | A kind of application of eight yuan of melon rings |
Non-Patent Citations (1)
| Title |
|---|
| QIAOXIAN HUANG等: "Alleviation of Polycation-Induced Blood Coagulation by the Formation of Polypseudorotaxanes with Macrocyclic Cucurbit[7]uril", 《AMERICAN CHEMICAL SOCIETY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111068102A (en) * | 2019-12-18 | 2020-04-28 | 陕西科技大学 | Enzyme-catalyzed blood-coagulation antibacterial controllable gelatin-based hydrogel and preparation method thereof |
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| CN109432090B (en) | 2020-10-23 |
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